Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: the Coronary Artery Risk Development in Young Adults Study.

OBJECTIVE: Determine associations of cardiorespiratory fitness, exercise systolic blood pressure (SBP) and heart rate recovery (HRR) following a maximal exercise test performed years preceding pregnancy with odds of preterm birth (PTB; <37 weeks' gestation) and small for gestational age (SGA; birthweight <10th percentile) delivery. DESIGN: Prospective, longitudinal. SETTING: Multi-site, observational cohort study initially consisting of 2787 black and white women aged 18-30 at baseline (1985-86) and followed for 25 years (Y25; 2010-2011). POPULATION: 768 nulliparous women at baseline who reported ≥1 live birth by the Y25 exam. METHODS: We used Poisson regression to determine associations of exposures with PTB/SGA. MAIN OUTCOME MEASURES: PTB and/or SGA births. RESULTS: Women with PTB (n = 143) and/or SGA (n = 88) were younger, had completed fewer years of education and were more likely to be black versus women without PTB/SGA (n = 546). Women with PTB/SGA had lower fitness (501 ± 9 versus 535 ± 6 seconds, P < 0.002) and higher submaximal SBP than women without PTB/SGA (144 ± 1 versus 142 ± 1 mmHg, P < 0.04). After adjustment, no exercise test variables were associated with PTB/SGA, though the association with HRR and submaximal SBP approached significance in the subset of women who completed the exercise test <5 years before the index birth. CONCLUSIONS: Neither fitness nor haemodynamic responses to exercise a median of 5 years preceding pregnancy, were associated with PTB/SGA. These findings indicate excess likelihood of PTB/SGA is not detectable by low fitness or exercise haemodynamic responses 5 years preceding pregnancy, but exercise testing, especially HRR and submaximal SBP, may be more useful when conducted closer to the onset of pregnancy. TWEETABLE ABSTRACT: Exercise testing conducted >5 years before pregnancy may not detect women likely to have PTB/SGA.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

Changes in procoagulants track longitudinally with insulin resistance: findings from the coronary artery risk development in young adults (CARDIA) study.

AIMS: To examine the association between changes in procoagulants (fibrinogen factors VII and VIII and von Willebrand factor) and the risk of insulin resistance. METHODS: Using data from the Coronary Artery Risk Development in Young Adults study, we followed 2398 black and white adults without diabetes, aged 25-37 years at year 7, to year 20. Levels of fibrinogen factors VII and VIII and von Willebrand factor were divided in tertiles (low/middle/high) at years 7 and 20 and four groups reflecting changes were defined: 'low' (low at years 7 and 20), 'stable' (low/middle at years 7 and 20, but not both low at years 7 and 20), 'high' (high at year 7 and low/middle at year 20; or low/middle at year 7 and high at year 20) and 'highest' (high at years 7 and 20). Linear regression models were used to evaluate 13-year changes (year 20-year 7) in fibrinogen level and factors VII, VIII and von Willebrand change groups in relation to insulin resistance measures. RESULTS: Homeostasis model assessment of insulin resistance (year 20) and changes in log homeostasis model assessment of insulin resistance (year 20-year 7) were significantly associated with the 13-year increase in fibrinogen (P < 0.001). Compared with participants in the low group, those in the high group had significantly higher levels of homeostasis model assessment of insulin resistance (year 20) and changes in homeostasis model assessment of insulin resistance (year 20-year 7) for fibrinogen factor VII and von Willebrand factor (P < 0.017). No significant associations were observed between fibrinogen VIII and insulin resistance measures. CONCLUSIONS: An increase in fibrinogen level and persistently high levels of factor VII and von Willebrand factor are significantly associated with increased risk of insulin resistance. These findings provide new insight into the mechanisms to explain the heightened risk for thrombosis in adults with insulin resistance/diabetes.

Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease.

BACKGROUND: Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. AIM: To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. METHODS: Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. RESULTS: In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (P<.05) and proctitis in ulcerative colitis (P<.05). CONCLUSIONS: SNPs associated with smoking quantity is associated with an increased risk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease.

Older women with diabetes have an increased risk of fracture: a prospective study.

To determine whether type 2 diabetes is associated with fracture in older women, we analyzed data from 9654 women, age 65 yr or older, in the Study of Osteoporotic Fractures. Diabetes with age at onset 40 yr or older was reported by 657 women, of whom 106 used insulin. A total of 2624 women experienced at least one nonvertebral fracture during an average follow-up of 9.4 yr, and 388 had at least one vertebral fracture during an average interval of 3.7 yr. Although diabetes was associated with higher bone mineral density, it was also associated with a higher risk of specific fractures. Compared with nondiabetics, women with diabetes who were not using insulin had an increased risk of hip [relative risk (RR), 1.82; 95% confidence interval (CI), 1.24-2.69] and proximal humerus (RR, 1.94; 95% CI, 1.24-3.02) fractures in multivariate models controlling for age, body mass index, bone density, and other factors associated with fractures and diabetes. Insulin-treated diabetics had more than double the risk of foot (multivariate adjusted RR, 2.66; 95% CI, 1.18-6.02) fractures compared with nondiabetics. This study indicates that diabetes is a risk factor for hip, proximal humerus, and foot fractures among older women, suggesting that fracture prevention efforts should be a consideration in the treatment of diabetes.

Evaluation of magnetic resonance imaging for quantification of intraabdominal fat in human beings by spin-echo and inversion-recovery protocols.

We evaluated two magnetic resonance imaging (MRI) methods, spin echo and inversion recovery (IR), for quantification of intraabdominal fat in a subgroup of participants from the Atherosclerosis Risk in Communities (ARIC) Study. Both methods were used previously to quantify visceral fat, and the IR but not the spin echo method has been validated by comparison with computed tomography in human beings. In the present study, the reliability of both methods was excellent: reliability coefficients comparing two readers on the same scan were 0.9574 for IR (n = 158) and 0.9254 for spin echo (n = 47) when random effects models with log-transformed data were used. A comparison of visceral fat areas in 47 subjects with both IR and spin echo indicated that IR gave a slightly higher mean area than did spin echo: 134.9 compared with 129.8 cm2. However, a mixed-model analysis of variance (ANOVA) of the log-transformed data showed no statistical difference between either method or readers in the comparison of IR and spin echo. These data suggest that the IR and spin echo protocols evaluated in this communication are comparable with one another and reliable for estimation of intraabdominal fat.

Lipoprotein(a) interactions with lipid and non-lipid risk factors in patients with early onset coronary artery disease: results from the NHLBI Family Heart Study.

BACKGROUND: A positive interaction between high plasma lipoprotein(a) [Lp(a)] and unfavorable plasma lipid levels has been reported to result in very high risk for premature coronary artery disease (CAD). We further examined this issue for men and women with early onset CAD. We also examined potential interactions between Lp(a) and non-lipid risk factors. METHODS AND RESULTS: In 338 men and women with early onset CAD (most with a positive family history of early CAD) and 480 general population controls, we measured Lp(a), lipids and other risk factors. In univariate analysis, relative odds for CAD was 1.7 (P = 0.002) for plasma Lp(a) >50 mg/dl. Elevated Lp(a) level was found to interact with adjusted plasma total/high density lipoprotein (HDL) cholesterol such that when Lp(a) was over 50 mg/dl and adjusted plasma total/HDL cholesterol >5.8, relative odds for CAD were 8.0-9.6 (P<0.0001) in multiple logistic regression. Non-lipid risk factors were generally found to multiply the risk associated with Lp(a) (as predicted by logistic regression) without evidence for interaction. CONCLUSIONS: We find evidence that Lp(a) does interact positively with adjusted plasma total/HDL cholesterol ratio. Aggressive risk factor intervention, especially for lipids, in those with elevated Lp(a) therefore appears indicated.

Blood pressure and menopausal transition: the Atherosclerosis Risk in Communities study (1987-95).

OBJECTIVE: Blood pressure changes during menopausal transition have not been studied previously using a biracial sample. We investigated whether menopausal transition was associated with change in blood pressure in African-American or white women. DESIGN, SETTING AND PARTICIPANTS: The prospective multicenter study, the Atherosclerosis Risk In Communities (ARIC) Study (1987-95) was utilized. Included were never-users of hormone replacement therapy (3,800 women, 44% of the original sample). MAIN OUTCOME MEASURE: Changes in blood pressure were adjusted for baseline age and body mass index, baseline blood pressure, antihypertensive use, ARIC field center and weight change. The menopausal transition group was compared to the non-transition group, separately, by ethnicity. RESULTS: Women undergoing the menopausal transition did not differ significantly in regard to systolic blood pressure change [5.2, 95% confidence interval (CI) 4.0-6.4] from non-transitional women (4.6, 95% CI 4.0-5.2); adjustment for age, baseline systolic blood pressure and other factors did not alter this finding. Transitional women had significantly less diastolic blood pressure change (-0.5, 95% CI -1.1 to 0.2) than non-transitional women (-2.0, 95% CI -2.4 to -1.7, P= 0.000) but, after adjustment for other covariates, the result was not significant African-American women had significantly (P= 0.003) higher systolic blood pressure change compared to white women, but this difference became non-significant (P= 0.21) after restricting the sample to women younger than 55 years of age. Interactions between menopausal transition and ethnicity were not significant, either in systolic blood pressure or diastolic blood pressure change. CONCLUSION: Menopausal transition is not associated with significant blood pressure change in African-American or white women.

Association of ventricular premature complexes with electrocardiographic-estimated left ventricular mass in a population of African-American and white men and women (The Atherosclerosis Risk in Communities.

Increased left ventricular (LV) mass is often found in adults and is a powerful predictor of cardiovascular mortality. To test the hypothesis that an electrocardiographic estimate of LV mass--the Cornell voltage--is associated with ventricular premature complexes (VPCs) in free-living adults, a cross-sectional analysis of the predictors of VPCs on a 2-minute rhythm strip in a population-based sample of 13,606 middle-aged, African-American and white men and women from 4 US communities in the Atherosclerosis Risk in Communities Study baseline examinations was performed. In adults without known coronary artery disease, the prevalence of VPCs increases monotonically with increasd Cornell voltages within ethnicity and gender groups. Independent of systemic hypertension, serum electrolytes, age, heart rate, educational attainment, gender, and ethnicity, a millivolt increase in Cornell voltage was associated with a 20% to 30% increase in the prevalence odds ratio of VPCs on the 2-minute electrocardiogram. Thus, Cornell voltage is associated with VPCs on a 2-minute electrocardiogram. The association is consistent in African-Americans, whites, men, and women.

Lipoprotein(a) as a correlate of stroke and transient ischemic attack prevalence in a biracial cohort: the ARIC Study. Atherosclerosis Risk in Communities.

Although both mean lipoprotein(a) [Lp(a)] concentration and national stroke prevalence estimates are consistently higher in American blacks than in whites, no information exists on the relationship of Lp(a) and stroke prevalence in African-Americans. Associations of Lp(a) with stroke or transient ischemic attack (TIA) are addressed in this report for 15,160 participants--4160 blacks and 11,000 whites--in the Atherosclerosis Risk in Communities (ARIC) Study. Lp(a) was measured in ARIC as its total protein component by double-antibody enzyme-linked immunosorbent assay (ELISA) for apo(a) detection. Self-reported stroke/TIA history was assessed as part of a standardized questionnaire, and resulted in age-adjusted stroke/TIA prevalences of 3.0% in blacks (n = 120) and 2.0% in whites (n = 222). Overall, mean Lp(a) protein levels were markedly higher for blacks than for whites (160.5 versus 81.6 micrograms/mL, respectively), and were statistically significantly higher among individuals reporting stroke/TIA history for both races (191.3 versus 159.6 micrograms/mL in blacks; 100.6 versus 81.2 micrograms/mL in whites). Multivariable logistic regression analysis for the association of Lp(a) protein with stroke/TIA status yielded a prevalence odds ratio (OR) (95% confidence intervals) of 1.17 (1.05, 1.30) overall (based on one standard deviation difference, 108.2 micrograms/mL, in Lp[a] protein). Race-specific ORs, after adjustment for the same covariates, were equivalent for blacks [OR = 1.17 (0.99, 1.39)] and whites [OR = 1.19 (1.04, 1.36)]. These data suggest that Lp(a) is an independent risk factor for stroke/TIA in both blacks and whites, and that the relative risk of stroke/TIA associated with Lp(a) protein does not vary by race.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults.

PURPOSE: Many epidemiologic studies have identified elevated plasma homocyst(e)ine as a risk factor for atherosclerosis and thromboembolic disease. To examined the relationship between vitamin intakes and plasma homocyst(e)ine, we analyzed dietary intake data from a case-control study of 322 middle-aged individuals with atherosclerosis in the carotid artery and 318 control subjects without evidence of this disease. METHODS: All of these individuals were selected from a probability sample of 15,800 men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: Plasma homocyst(e)ine was inversely associated with intakes of folate, vitamin B6, and vitamin B12 (controls only for this vitamin)--the three key vitamins in homocyst(e)ine metabolism. Among nonusers of vitamin supplement products, on average each tertile increase in intake of these vitamins was associated with 0.4 to 0.7 mumol/L decrease in plasma homocyst(e)ine. An inverse association of plasma homocyst(e)ine was also found with thiamin, riboflavin, calcium, phosphorus, and iron. Methionine and protein intake did not show any significant association with plasma homocyst(e)ine. CONCLUSIONS: In almost all analyses, cases and controls showed similar associations between dietary variables and plasma homocyst(e)ine. Plasma homocyst(e)ine among users of vitamin supplement products was 1.5 mumol/L lower than that among nonusers. Further studies to examine possible causal relationships among vitamin intake, plasma homocyst(e)ine, and cardiovascular disease are needed.

Seven-year changes in physical fitness, physical activity, and lipid profile in the CARDIA study. Coronary Artery Risk Development in Young Adults.

PURPOSE: To relate seven year changes in physical fitness and physical activity in the young adult population to changes in the plasma lipid profile and to examine the influence of weight change on those relationships. METHODS: The participants in this observational study were the 1777 black and white men and women, ages 18-30 at entry into the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, who completed a symptom-limited graded treadmill exercise test and had an overnight fasting blood draw at both the Baseline (1985-86) and Year 7 (1992-93) exams. CARDIA, a longitudinal study of the relationships of lifestyle and physiological variables to the development of coronary heart disease risk factors, consists of population-based cohorts in Birmingham, Alabama, Minneapolis, Minnesota and Chicago, Illinois and a cohort recruited from the membership of a large, pre-paid health care plan, broadly representative of the population, in Oakland, California. RESULTS: All race/gender groups experienced mean decreases in physical fitness and self-reported physical activity and increases in weight. Decreased fitness was associated with decreased high density lipoprotein-cholesterol (HDL-C), and conversely, increased fitness was associated with increased HDL-C. The correlation coefficients of change in fitness with change in HDL-C ranged from 0.17 in white men and black women to 0.24 in white women (P < 0.001 for all race/gender groups). Change in fitness was minimally correlated with change in low density lipoprotein-cholesterol (LDL-C) in all groups (r ranged from -0.09 in black women to -0.20 in white women), triglycerides (TG) in men and white women (r ranged from -0.10 to -0.15), and total cholesterol (TC) in white men and women (r = -0.11 and -0.15, respectively). The magnitude of these correlations was further reduced with adjustment for weight change. Correlations between change in activity and change in lipid and lipoprotein values were generally weak or nonexistent, except for the suggestion of a small, direct relationship with change in HDL-C in black and white women (r = 0.14 and r = 0.11, respectively). All of the weight change adjusted correlations were essentially unaffected by further adjustment for baseline fitness or activity and other covariates. CONCLUSIONS: Decreased fitness during young adulthood is associated with unfavorable changes in lipid profile, explained mostly by increased weight. Lack of association between change in activity and change in lipid profile observed in this study may be due, in part, to imprecision of activity measurement.

The Family Risk Score for coronary heart disease: associations with lipids, lipoproteins, and body habitus in a middle-aged bi-racial cohort: The ARIC study.

PURPOSE: To examine the association between the Family Risk Score (FRS) for coronary heart disease (CHD) and body mass index (BMI), waist-to-hip ratio (WHR), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein(a) protein [Lp(a)]. METHODS: FRS was computed from observed and expected CHD events using family data collected from 11467 black and white adults of the Atherosclerosis Risk in Communities Study (ARIC). BMI, WHR, and lipids adjusted for study center, race, education, BMI (except BMI), WHR (except for BMI and WHR), cigarette smoking, alcohol, and Keys' score were compared among low (FRS < -0.5), average (-0.5 to 0.5), and high (> 0.5) FRS using analysis of covariance. The association between FRS and these risk factors was compared to that for simpler estimates of family risk. RESULTS: Adjusted means of BMI, WHR, LDL, LP(a), and triglycerides were positively associated with FRS, whereas HDL cholesterol was inversely associated with FRS. Of demographic and behavioral factors, cigarette smoking was most strongly associated with FRS. Based on additional comparisons of adjusted means, high vs. low levels of FRS appear to correlate better with CHD risk factors than do the simpler family history assessments. CONCLUSIONS: In situations were genetic or clinical information is not available, FRS may be a favorable measure of familial burden for CHD.

The relationship between lipids/lipoproteins and atherosclerosis in African Americans and whites: the Atherosclerosis Risk in Communities Study.

PURPOSE: The relationships between lipids/lipoproteins and atherosclerosis were determined in African Americans and whites to assess the consistency of the relationship between these two groups. Differences could suggest varying biological, environmental, or life-style cofactors influencing development of atherosclerosis. METHODS: In the Atherosclerosis Risk in Communities Study, 2966 African Americans and 9399 whites had determinations of LDL, HDL, HDL2, and HDL3 cholesterol, triglycerides, apolipoprotein A1 and B, and lipoprotein (a). Carotid intimal-medial thickening (IMT) was measured using B-mode ultrasound imaging. RESULTS: The associations, using linear regression, between carotid IMT and LDL cholesterol, HDL cholesterol, and other lipid measurements were significantly weaker in African Americans than whites. Averaging men and women, a 1.034 mmol/L (40 mg/dl) difference in LDL cholesterol was associated with a 0.028 mm IMT difference in whites but a 0.019 difference in African Americans. Similarly, for HDL cholesterol, a 0.44 mmol/L (17 mg/dl) difference is associated wth 0.026 mm difference in carotid IMT in whites and 0.011 mm difference in African Americans. The associations are much weaker in African Americans than whites at the bifurcation and internal carotid, the carotid sites most prone to atherosclerosis. Analysis was done stratifying for risk factors that differ between African Americans and whites, but within most, the relationships remained substantially weaker in African Americans. CONCLUSIONS: We have observed a statistically significant difference in the association between many lipids/lipoproteins and carotid IMT between African Americans and whites. Analysis of many potential cofactors have not provided an explanation for the weaker association. Although possible differences in prior levels of these lipids may provide one explanation for the finding, these results need confirmation in other studies.

Independent and interactive effects of apolipoprotein E phenotype and cardiorespiratory fitness on plasma lipids.

PURPOSE: To examine whether the association Apolipoprotein E (Apo E) phenotype with plasma lipids is influenced by physical fitness level. Also, to explore the interactive and independent relative contributions of Apo E phenotype, fitness (or physical activity), and other modifiable factors to variation in plasma low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) levels at baseline and over a seven-year follow-up. METHODS: Physical fitness (duration of a graded treadmill test), Apo E phenotype, plasma LDL-C and HDL-C, and covariates were measured at baseline and seven years later in a bi-racial cohort of young adults, aged 18-30 years at baseline in 1985-86, from the Coronary Artery Risk Development In Young Adults (CARDIA) study. RESULTS: Fitness did not influence the associations of Apo E and LDL-C or HDL-C. The independent effects of several modifiable variables (changes in Keys' score, smoking, oral contraceptive use, education, body weight, alcohol intake, and fitness), when combined, contributed considerably more than Apo E to the variance in LDL-C changes (6.74% or 8.71% for combined modifiable variables vs. 1.27% or 0.90% for ApoE, in women or men, respectively) and HDL-C changes (13.11% or 12.66% for combined modifiable variables vs. 0.12% or 0.02% for ApoE, in women or men, respectively). The pattern of findings was similar when self-reported physical activity was substituted for fitness. CONCLUSIONS: Changes in modifiable factors, including fitness, may be stronger correlates of changes in LDL-C and HDL-C over time than the immutable factor, Apo E phenotype.

Reliability of near-infrared interactance body fat assessment relative to standard anthropometric techniques.

We examined the repeatability of near-infrared interactance (NIR) body fat determination as compared with that of body mass index (BMI), waist-to-hip ratio (WHR), and waist girth. Thirty-nine volunteers (16 men, 23 women) had percent body fat (%BF) measurements made with a portable NIR device as well as the standard anthropometric indices of height, weight, waist girth, and hip circumference. Frame size and physical activity levels were also determined. For each participant, three independent measurements of each index were made by two trained readers during a 2-week period. The two readers varied significantly in their measurement of %BF and hip circumference. The variability in %BF was largely due to differences between the first and the second measurements, and only for one of the readers. Second and third measurements were not statistically significantly different for either reader, suggestive of a training effect. Variance component calculations revealed that the reliability of NIR is 95.3%, compared with 99.9% for BMI; 93.4% for waist girth; and 82.4% for WHR, with the majority of the remaining variance accounted for by the method itself. We conclude that the NIR method has good repeatability, with low intra- and interobserver variability, provided that readers are carefully trained. However, the NIR device offers little advantage in reliability over conventional measures of adiposity such as waist girth or BMI, and requires additional input of weight, height, frame size, physical activity level, age, and gender data to calculate %BF. Associations of NIR and other anthropometric indices with cardiovascular risk factors in this population will provide additional insight into the merit of NIR body fat assessment.

Validity of self-reported fat distribution in young adults: the CARDIA Study. Coronary Artery Risk Development in Young Adults.

To determine the validity of self-reported information on body fat distribution, relationships between reported location of weight gain and measured waist-to-hip ratio (WHR), high density lipoprotein cholesterol (HDL-C), and fasting insulin were analyzed in 5115 black and white men and women aged 18-30 years. In black men, WHR adjusted for age and body mass index (BMI) ranged from 0.833 among those reporting upper and central weight gain to 0.812 among those reporting lower body weight gain (trend across five reported fat distribution categories, P = 0.0004). Corresponding values were, for white men, 0.852 to 0.831; for black women, 0.777 to 0.721; and for white women, 0.772 to 0.701 (each P < 0.0001). Reported fat distribution was associated with HDL-C in women, but not in men, and with fasting insulin in all groups. While these associations were somewhat weaker than with measured WHR, self-reported fat distribution does provide valid information about body fat distribution in young adults, particularly women.

Repeatability and validity of the Rose questionnaire for angina pectoris in the Atherosclerosis Risk in Communities Study.

Angina pectoris (AP) as determined by the Rose questionnaire was assessed in nearly 16,000 black and white men and women participating in the Atherosclerosis Risk in communities Study, a population study of cardiovascular disease in four communities. The questionnaire was administered at yearly intervals and estimates of repeatability were made. Validity was assessed indirectly by comparing Rose AP to risk factors, prevalent heart disease, medication use, and thickness of carotid artery walls as measured by B-mode ultrasound. Using kappa statistics for agreement of positive Rose AP determinations taken 1 year apart, white men show a higher level of agreement than white women (average kappa 0.36 for white men, 0.30 for white women), and whites show a higher level of agreement than blacks (average kappa 0.23 and 0.22 for black men and women, respectively). Rose AP that persists for more than one determination is associated with thicker carotid artery walls, greater amounts of cigarette smoking, greater prevalence of reported heart attack, and greater use of chest pain medications. A single determination of severe Rose AP is also associated with thicker carotid artery walls. These data suggest that multiple reports and the more severe grading of Rose AP (pain reported while walking on the level) are likely to indicate more severe disease; however, a single report using the Rose questionnaire appears valid, i.e., moderately associated with disease and risk factors, and appropriate for use in epidemiological studies.

Social service interventions for caregivers of patients with dementia: impact on health care utilization and expenditures.

OBJECTIVES: An intervention, which had as its primary goal the enhancement of compliance to social work recommendations, was shown to produce extremely high rates of compliance. This report addresses the secondary objective of the study: to evaluate the impact of the intervention on short-term (ie, 6-month) health services utilization and expenditures. DESIGN: Randomized controlled trial. SETTING: University-based memory disorders clinic. PARTICIPANTS: Caregivers of patients with progressive memory disorders. MAIN OUTCOME MEASURES: Service utilization and expenditures. RESULTS: The intervention did not have a statistically significant impact on utilization of either health care or community resources. The intervention group had $903 less expenditures during the study period, a difference that did not achieve statistical significance. The results were consistent when controlling for caregiver characteristics that differed at baseline. CONCLUSIONS: Although the intervention was successful in enhancing compliance with recommendations, more intensive interventions may be required to increase subsequent service utilization. Future investigations may wish to target the appropriateness of services used over a period longer than 6 months.

Intramolecular 4 + 3 cycloadditions. A theoretical analysis of simple diastereoselectivity in reactions of alkoxyallylic cations and furans.

[reaction--see text] A computational examination (B3LYP/6-31+G*//HF/6-31+G* + ZPVE) of an intramolecular 4 + 3 cycloaddition reaction suggests a stepwise process and the likelihood of reversibility in at least one of the pathways examined.