Biomedical subjects

Gail A Laughlin

Publications and source records attributed to Gail A Laughlin.

15 recordsLinked to original sources

PubMed2006

Coronary artery calcium versus intima-media thickness as a measure of cardiovascular disease among asymptomatic adults (from the Rancho Bernardo Study).

Detection and quantification of subclinical coronary heart disease by noninvasive imaging techniques offers the potential for earlier diagnosis with targeted prevention and therapy. This study, designed to determine the extent to which carotid artery intima-media thickness (IMT) predicts coronary artery calcium (CAC) in asymptomatic older adults, included 141 men and 137 women > or =55 years of age with no previous coronary heart disease who had B-mode ultrasound of the common and/or internal carotid arteries in 1997 to 1999 to measure IMT and electron beam computed tomographic scanning in 2001 to 2002 to measure CAC score. Overall, 29% of participants had a severe plaque burden (CAC score >400); 50% of these had a CAC score >800. IMT of the common and internal carotid arteries was significantly associated with the CAC score measured an average of 3 years later. The ability to correctly identify subjects with a severe CAC score (sensitivity) was 50% to 60% for an IMT of the internal or common carotid artery > 80th percentile (internal carotid IMT > or =1.9 mm and common carotid IMT > or =1.04 mm). Specificity, the ability to correctly identify those who did not have a severe CAC score (> or =400), was approximately 75%. In conclusion, IMT of the carotid arteries predicted the severity of CAC burden an average of 3 years later in community-dwelling asymptomatic older adults.

Aged↗

PubMed2006

Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study.

Hypoadiponectinemia has been implicated in the development of obesity-related conditions, including dyslipidemia and coronary heart disease (CHD). In this study, the authors examined the association of adiponectin with CHD prevalence, incidence, and mortality among 1,513 community-dwelling men and women aged 50-91 years who were followed from 1984-1987 through 2004. In cross-sectional analyses, adiponectin concentrations were positively related to female sex, age, and high density lipoprotein cholesterol level and inversely related to waist girth, triglyceride level, and fasting plasma glucose level (all p's < 0.001). Adiponectin levels in the highest sex-specific quintile, as compared with the lowest, were associated with 44% decreased odds of prevalent CHD (p for trend = 0.03); adjustment for high density lipoprotein cholesterol and/or triglycerides eliminated this association. In 20-year prospective analyses, higher adiponectin concentrations predicted reduced risk of nonfatal myocardial infarction in men only; adiponectin was not associated with fatal incident CHD events or 20-year CHD mortality (n = 215 deaths) in either sex. Adiponectin levels in the highest sex-specific quintile, as compared with lower levels, were associated with almost 40% increased risks of cardiovascular disease death (n = 441) and death from all causes (n = 925), independent of age, sex, waist girth, lipid levels, and glucose level (both p's < 0.001). These results suggest that use of adiponectin for cardiovascular disease risk stratification is premature.

Adiponectin↗

PubMed2006

Association between the ankle-brachial index and carotid intimal medial thickness in the Rancho Bernardo Study.

Previous cross-sectional studies have demonstrated significant associations between the ankle-brachial index (ABI) and carotid intimal medial thickness (IMT). In a longitudinal study, 637 participants who had ABI measurements from 1992 to 1994 were tested for carotid IMT an average of 4.8 years later. Mean age was 72.5 years; 60% were women. More than half (51%) were hypertensive, whereas 28% had dyslipidemia, 56% were past or current smokers, and 6% had diabetes. The mean +/- SD ABI and IMT were 1.06 +/- 0.13 and 1.28 +/- 0.44 mm, respectively. Mean age- and gender-adjusted IMTs for the ABI groups of <or=0.90, 0.91 to 0.99, and 1.00 to 1.09 were significantly greater than those from 1.10 to 1.26 (1.53, 1.49, 1.28, and 1.18 mm, respectively, p <0.05 for all). In logistic regression analyses, each of these ABI groups was significantly associated with increased odds for an IMT in the highest decile compared with an ABI of 1.10 to 1.26 (odds ratios 3.2, 4.3, and 2.3, respectively, p <0.05 for all). In conclusion, an ABI of 1.10 to 1.26 was associated with the lowest levels of cardiovascular disease risk factors and carotid atherosclerosis, suggesting that a new cut point for ABI risk stratification should be considered.

Aged↗

PubMed2006

The Dehydroepiandrosterone And WellNess (DAWN) study: research design and methods.

Levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), the major secretory products of the adrenal gland, decline dramatically with age, concurrent with the onset of degenerative changes and chronic diseases associated with aging. Epidemiological evidences in humans and animal studies suggest that DHEA(S) may have cardioprotective, antiobesity, antidiabetic, and immuno-enhancing properties. These observations led to the proposal that restoration of DHEA to young adult levels may have beneficial effects on age-related conditions. Most clinical trials of DHEA replacement have been limited due to small samples and short duration, restriction to one sex, failure to adjust for baseline endogenous hormone level and age, or lack of placebo comparison groups. We designed a double blind, placebo-controlled randomized trial to determine the acceptability, benefits, and adverse effects of 50 mg daily oral DHEA replacement for one year in 110 men and 115 women, aged 55 to 85, who were healthy and not currently using hormone therapy. A wide range of biological outcomes were studied including bone mineral density and metabolism, body composition and muscle strength, immune function, and cardiovascular risk factors. Steroid hormone levels, bone markers, cytokines, and the IGF-I, IGF binding protein system were measured at baseline and at 3 follow-up clinic visits. Changes in mood and well-being, cognitive function, and sexuality were assessed. Information on potentially confounding covariates such as smoking, alcohol consumption, exercise, diet and dietary supplements were obtained, and potential adverse effects of DHEA administration were monitored. This study enables an examination of the benefits of DHEA administration on the health of older men and women, and the influence of gender, age, and baseline endogenous DHEA level on each outcome variable. Potential mechanisms of DHEA action, including the biotransformation of DHEA to active steroids and steroid metabolites, enhancement of IGF-I bioavailability, and inhibition of IL-6 production can also be evaluated.

Adjuvants, Immunologic↗

PubMed2006

Sex-specific association of the androgen to oestrogen ratio with adipocytokine levels in older adults: the Rancho Bernardo Study.

OBJECTIVE: Androgens and oestrogens have opposing effects on some adipocyte functions. Thus, the androgen to oestrogen balance may be as important as the individual hormones in determining the biological interaction between endogenous sex hormones and adipocyte-derived factors such as adiponectin and leptin. We tested this hypothesis by evaluating the sex-specific, cross-sectional association of sex hormones and androgen to oestrogen ratios with serum adiponectin and leptin in older men and postmenopausal women. DESIGN: Cross-sectional. PARTICIPANTS: A total of 1510 community dwelling men and postmenopausal women aged 50-92 years. MEASUREMENTS: Serum leptin, adiponectin and sex hormone levels. RESULTS: Adiponectin and leptin levels were higher in women than men (P < 0.001). In both sexes, adiponectin concentrations were lower, and leptin levels higher, with increasing BMI and waist girth (all P < 0.001). Although the ratio of total testosterone to total oestradiol was significantly associated with both adipocytokines in both sexes, the strongest and most consistent hormone-adipocytokine associations were observed when the androgen to oestrogen ratio was expressed as total testosterone to bioavailable oestradiol. In linear regressions, the testosterone to bioavailable oestradiol ratio was positively related to adiponectin and inversely related to leptin, with nearly identical standardized beta-coefficients for men and women (all P < 0.001). The strength of the hormone ratio-adipocytokine associations was reduced, but not eliminated, after adjustment for age, adiposity and cardiovascular disease risk factors, including insulin resistance. CONCLUSIONS: The striking similarity of the hormone ratio-adipocytokine associations for men and women, despite wide differences in sex hormone and adipocytokine levels, suggests these results reflect underlying physiological mechanisms common to both sexes.

Adiponectin↗

PubMed2006

Electron beam computed tomography screening and heart disease risk factor modification.

The authors examined the effect of electron beam computed tomography screening on perceived risk, behavior change, and medical intervention among community-dwelling adults with no history of heart disease. Participants were 184 men and 180 women aged 55 years and older who had electron beam computed tomography scans in 2000-2001 and responded to a questionnaire 6 months later. They were classified as low-, medium-, or high-risk based on coronary artery calcification score, an indicator of coronary artery plaque burden. Overall, only 5% of participants were alarmed or quite worried about developing heart disease. Compared with those with lower risk, high-risk participants were more likely to discuss scan results with a physician, undergo further cardiac testing, have a cholesterol test (all p < 0.001), and begin cholesterol-lowering medication (p < 0.001), aspirin (p = 0.009), and multivitamins (p = 0.018). The authors conclude that electron beam computed tomography screening motivates initiation of measures to prevent clinical heart disease without causing undue alarm among older men and women.

Aged↗

PubMed2005

Association between the ankle-brachial index and future coronary calcium (the Rancho Bernardo study).

This study investigated whether the ankle-brachial index (ABI) is associated with coronary artery calcium (CAC) in a cohort of men and women who were free of clinical coronary heart disease. CAC was assessed by electron beam computed tomography in 279 community-based subjects who also had ABI measurements 7 years previously. Patients' mean age was 65.8 years and 51.3% were women. Thirty-three patients (11.8%) had an ABI < 1.0, 11 (3.9%) had an ABI < 0.9, and 4 (1.4%) had an ABI < 0.8. Prevalences of any CAC were 70% for women and 95% for men. In men and women, there was a U-shaped relation between CAC and ABI category, with the lowest CAC score being in the interval from 1.0 to 1.09. On multivariable analysis, women whose ABI was < 1.0 had a 2.7-fold higher risk (p = 0.03) for increasing amounts of CAC. Men whose ABI was below this same cutpoint had a similar but nonsignificant increase in risk (odds ratio 2.1, p = 0.1). In conclusion, ABI was significantly associated with the presence and extent of future CAC measured 7 years later.

Adult↗

PubMed2005

Differences in association of bone mineral density with coronary artery calcification in men and women: the Rancho Bernardo Study.

OBJECTIVE: Whether osteoporosis and calcification of atherosclerotic plaque are two independent, age-related processes or linked by similar mechanisms of bone mineralization and plaque calcification is unknown. This study examines the sex-specific association between bone mineral density (BMD) and coronary artery calcification with a particular focus on hormone therapy (HT). DESIGN: Participants were 180 men (aged 47-86 years) and 186 women (aged 58-81 years) without a history of heart disease who had hip and spine BMD assessed by dual-energy x-ray absorptiometry and coronary artery calcium score (CACS) measured by electron-beam computed tomography. Calcium scores were categorized into none/minimal ( or=400). Ordinal and binary logistic regressions examined the associations between site-specific BMD and CACS. RESULTS: In men and women not using HT, there was no age-independent association between BMD at any site and CACS. In contrast, among current HT users an inverse association of BMD with coronary artery calcification was observed at the total hip (odds ratio [OR] = 0.56, 95% CI, 0.33-0.95), trochanter (OR = 0.55, 95% CI, 0.32-0.93), and intertrochanter area (OR = 0.60, 95% CI, 0.41-0.86) after adjustment for age and other risk factors. Other skeletal sites showed similar, but not statistically significant, associations (P < 0.1). CONCLUSION: Lack of association between BMD and CACS in men and women not using HT and the inverse association in women on HT suggest that the association between coronary and bone calcium might be mediated by estrogen.

Absorptiometry, Photon↗

PubMed2005

Ghrelin, adiponectin, and leptin do not predict long-term changes in weight and body mass index in older adults: longitudinal analysis of the Rancho Bernardo cohort.

Ghrelin, leptin, and adiponectin are associated with body size in cross-sectional studies; it is unknown whether these hormones predict long-term changes in body size. Multilevel models were used to study associations between fasting serum hormones, measured in 698 men and 619 women (60-91 years) in samples collected at baseline (1984-1987), and changes in weight and body mass index, assessed repeatedly over a follow-up period of up to 18 years (median, 4.7 years). Baseline weight was -1.5 kg lower for a one-standard-deviation increment in ghrelin and -3.3 kg lower for a one-standard-deviation increment in adiponectin, similar in men and women. For leptin, baseline weight was 12.1 kg higher for a one-standard-deviation increment in men, compared with 5.7 kg in women (sex-interaction p < or = 0.0001). Ghrelin and adiponectin did not affect weight change; their associations with weight were constant over time, indicated by nonsignificant hormone-by-time interactions. The positive association between leptin and weight became slightly weaker over time. Results were similar when investigating repeated measures of body mass index. From this analysis of Rancho Bernardo Study data, the authors conclude that ghrelin, adiponectin, and leptin do not predict weight gain beyond reflecting the influence of attained body size on future changes in weight or body mass index.

Adiponectin↗

PubMed2005

Ghrelin and the metabolic syndrome in older adults.

CONTEXT: Ghrelin may be one of the pathophysiological mechanisms underlying risk factor clustering observed in the metabolic syndrome, but this has not been investigated. OBJECTIVE: The objective of this work was to study the association between ghrelin and the metabolic syndrome and identify social and behavioral determinants of ghrelin. DESIGN: This was a cross-sectional study. SETTING: The setting of this work was the Rancho Bernardo Study. PARTICIPANTS: Study subjects included 1513 men and women, aged 51-90 yr in 1984-1987. OUTCOMES: Total ghrelin, measured by RIA, and the metabolic syndrome, defined using Adult Treatment Panel III diagnostic criteria, were the outcome measures. RESULTS: Levels of ghrelin (mean +/- SD) did not differ between the 848 men (1451 +/- 532 pg/ml) and the 665 women (1459 +/- 672 pg/ml) or by age. Education, alcohol intake, and smoking history were each significantly and positively associated with ghrelin in a dose-related manner, independent of body mass index (BMI). Compared with participants with the lowest third of ghrelin levels, the age- and sex-adjusted odds of having the metabolic syndrome were 18% lower in the middle third and 53% lower in the highest third. This corresponds to a 21% decrease per SD increase in ghrelin (odds ratio, 0.79; 95% confidence interval, 0.69, 0.89; P < or = 0.001); this was attenuated to 13% (odds ratio, 0.87; 95% confidence interval, 0.75, 1.01; P = 0.07), after adjustment for BMI. Of the five metabolic syndrome components, only the association between ghrelin and high-density lipoprotein cholesterol was independent of BMI. A significant association independent of BMI was also observed between insulin and ghrelin. CONCLUSIONS: Ghrelin levels are influenced by lifestyle factors. The inverse association between endogenous ghrelin and the metabolic syndrome is largely explained by the strong ghrelin-BMI association.

Aged↗

PubMed2005

The association of endogenous sex steroids and sex steroid binding proteins with mammographic density: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study.

Mammographic density is an independent risk factor for breast cancer. In postmenopausal women, higher levels of endogenous sex steroids are associated with an increased risk of breast cancer. Limited prior data suggest that endogenous sex steroids either are not associated (total estradiol and progesterone) or are negatively associated (free estradiol) with higher mammographic density. To analyze the associations between endogenous sex steroids and mammographic density, the authors conducted a 1998-2005 cross-sectional analysis of baseline clinical trial data from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial for US women who had not used hormone therapy for at least 3.1 months prior to baseline. In models adjusted for age, body mass index, parity, prior use of hormone therapy, time since last use of hormone therapy, and the interaction between prior hormone therapy use and time since last hormone therapy use, higher levels of estrone (beta = 0.0013, p = 0.014), estradiol (beta = 0.0009, p = 0.009), and bioavailable estradiol (beta = 0.0021, p = 0.018) were statistically significantly related to greater mammographic density. (Beta coefficients express the increment in mammographic density per-unit increment (pg/ml) of each hormone.) These results suggest that some sex steroids may increase the risk of breast cancer by stimulating breast epithelial or stromal proliferation, which appears on a mammogram as higher density.

Breast↗

PubMed2004

The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-1 levels with all cause and cardiovascular disease mortality in older adults: the Rancho Bernardo Study.

The IGF system has been implicated in cardiovascular disease (CVD) development. The prospective association of serum IGF-I and IGF-binding protein-1 (IGFBP-1) with all cause, ischemic heart disease (IHD), and non-IHD CVD mortality was examined in 633 men and 552 nonestrogen-using postmenopausal women, aged 51-98 yr (mean, 74 yr) in 1988-1992, who were followed through July 2001 (96% follow-up). During the 9- to 13-yr follow-up, there were 522 deaths; 224 were attributed to CVD, and 105 were caused by IHD. IGF-I and IGFBP-1 were independently and jointly related to risk of IHD mortality. In a proportional hazards model including both IGF-I and IGFBP-1 and adjusting for CVD risk factors, the relative risk of IHD mortality was 38% higher for every 40 ng/ml (1 SD) decrease in IGF-I (95% confidence interval, 1.09-1.76; P = 0.005) and 3.11 times greater for those in the lowest quintile of IGFBP-1 (95% confidence interval, 1.74-5.56; P < 0.001) compared with those with higher IGFBP-1 levels. IGF-I and IGFBP-1 (alone or in combination) were not related to risk of all cause or non-IHD CVD mortality. We conclude that low baseline levels of IGF-I and IGFBP-1 increase the risk of fatal IHD among elderly men and women independent of prevalent IHD and CVD risk factors.

Age Factors↗

PubMed2004

A longitudinal study of dehydroepiandrosterone sulphate (DHEAS) change in older men and women: the Rancho Bernardo Study.

OBJECTIVE: To examine the age-related and sex-specific rates and determinants of change in endogenous dehydroepiandrosterone sulphate (DHEAS) levels in older community-dwelling adults, taking into account regression to the mean. DESIGN: Prospective cohort study from Rancho Bernardo, California, USA. METHODS: Plasma for DHEAS was collected at baseline and 10-14 years later from 242 men and 207 postmenopausal women (age range, 60-77 years), who were not taking hormone therapy or corticosteroids. Age-related and sex-specific changes in DHEAS were calculated according to four different definitions of change: absolute change, annual percentage change, change exceeding 10% of baseline and change exceeding that expected from statistical regression to the mean. Determinants of DHEAS change were assessed using regression analyses. RESULTS: Baseline DHEAS levels were higher for men than women (age-adjusted means, 1.37+/-0.73 microg/ml (3.72+/-1.98 micromol/l) vs 0.73+/-0.48 microg/ml (1.98+/-1.30 micromol/l) respectively, P<0.0001), with more pronounced declines observed in men (-4.0%/year) compared with women (-2.1%/year; P<0.001). Some 28% of women and 5% of men had DHEAS levels that increased or stayed the same according to a 10% definition of change. When regression to the mean artifact was accounted for, only 15% of women and 5% of men showed true increases in DHEAS. In both sexes, baseline DHEAS levels accounted for three-quarters of the variability in absolute DHEAS change over time, with higher baseline levels resulting in greater loss. Sex, baseline weight, age and smoking status were significantly associated with DHEAS change in univariate models; only sex remained independently associated with DHEAS change in multivariate analyses, with men showing greater annual declines than women (estimated coefficient=0.006, P=0.008). CONCLUSION: In this sample, over 30% of the observed changes in DHEAS could be attributed to regression to the mean. Potential underlying mechanisms of change in DHEAS levels, and sex differences, are discussed.

Aged↗

PubMed2003

Association of endogenous sex hormones and insulin resistance among postmenopausal women: results from the Postmenopausal Estrogen/Progestin Intervention Trial.

Most studies of sex hormones and insulin resistance (IR) have focused on androgens; few have examined the association of endogenous estrogens and IR. We determined the cross-sectional association of endogenous levels of total and bioavailable testosterone and estradiol and SHBG with IR among 845 healthy, postmenopausal women aged 45-65 yr. Women were within 10 yr of menopause and not using hormone replacement therapy. Total adiposity was estimated by body mass index, visceral adiposity by waist to hip ratio (WHR), and IR by the homeostasis model assessment. We defined homeostasis model assessment-IR as the highest quartile (cutpoint, 2.1) of the distribution in this cohort. In logistic regression analyses, the odds for IR were significant and increased in a dose-response fashion across each quartile of total estradiol, bioavailable estradiol, and bioavailable testosterone (all P < 0.001 for linear trend). These associations remained significant after adjusting for WHR; adjusted odds ratios were 4.0, 6.1, and 2.7 for total estradiol, bioavailable estradiol, and bioavailable testosterone, respectively, comparing the highest to the lowest quartile (all P < 0.001). Adjusting for body mass index and WHR together eliminated the linear association of IR with total estradiol and bioavailable testosterone, but the association with bioavailable estradiol remained (adjusted odds ratio, 2.7; P < 0.001, comparing the highest to the lowest quartile). IR was not associated with total testosterone before or after adjusting for adiposity. Lower SHBG levels were associated with higher odds of IR, independent of adiposity. These results suggest that estrogen may be equally or more important than testosterone in the pathway to IR in healthy, young postmenopausal women, with differences not entirely explained by body size.

Adipose Tissue↗

PubMedDate not supplied

Hormone therapy and coronary artery calcification in asymptomatic postmenopausal women: the Rancho Bernardo Study.

OBJECTIVE: To determine (1) whether past or current hormone therapy (HT) in postmenopausal women is associated with subclinical coronary artery plaque burden, (2) whether any association is independent of age, body size, blood pressure, lipids, fasting plasma glucose, cigarette smoking, leisure time physical activity, alcohol intake, use of lipid-lowering medications, and socioeconomic status, and (3) whether any association varies by duration of HT or by the use of combined versus unopposed HT. DESIGN: An observational study, with HT validated and coronary heart disease risk factors determined between 1997 and 1999 in a research clinic, and coronary artery calcium score (CACS) evaluated by electron beam computed tomography in 2001 through 2002. Participants were 204 community-dwelling postmenopausal women from the Rancho Bernardo cohort aged 55 to 78 years with no history of heart disease. RESULTS: The odds of severe CACS in current estrogen users (n = 127) was 0.40 (95% CI 0.19, 0.82), controlling for all covariates. Past users (n = 40) had intermediate odds (multiply adjusted OR = 0.66, 95% CI = 0.28, 1.58). In subgroup analyses, age-adjusted associations did not differ between the 68 women using unopposed estrogen versus the 59 using an estrogen-progestin regimen. Women who had used HT for at least 10 years (n = 86) had significantly less (P = 0.01) plaque burden than shorter term users (n = 41). CONCLUSIONS: Both the strong association and the duration of use effect independent of lifestyle and social class suggest an antiatherogenic effect of postmenopausal estrogen. Only a clinical trial can completely exclude confounding by social class, lifestyle, and unmeasured covariates.

Age Factors↗