RESUMEN
BACKGROUND: Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen-Alone (E-Alone) trial, randomization to conjugated equine estrogen-alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI-CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post-trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors. METHODS AND RESULTS: WHI-CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age-adjusted rates/1000 person-years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2-fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen-alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality. CONCLUSIONS: Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E-Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen-alone versus placebo or CVD risk factors. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611.
Asunto(s)
Enfermedad de la Arteria Coronaria/epidemiología , Terapia de Reemplazo de Estrógeno/métodos , Estrógenos Conjugados (USP)/administración & dosificación , Calcificación Vascular/epidemiología , Salud de la Mujer , Distribución de Chi-Cuadrado , Angiografía por Tomografía Computarizada , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Terapia de Reemplazo de Estrógeno/efectos adversos , Terapia de Reemplazo de Estrógeno/mortalidad , Estrógenos Conjugados (USP)/efectos adversos , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Análisis Multivariante , Posmenopausia , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/mortalidadRESUMEN
BACKGROUND: Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury). METHODS AND RESULTS: The Cardiovascular Health Study Cognition Study was a continuation of the Cardiovascular Health Study limited to the Pittsburgh, PA, center from 1998-1999 to 2014. In 1992-1994, 924 participants underwent magnetic resonance imaging of the brain. There were 199 deaths and 116 developed dementia before 1998-1999. Of the 609 participants eligible for the Pittsburgh Cardiovascular Health Study Cognition Study, 87.5% (n=532) were included in the study. There were 120 incident HF cases and 72% had dementia. In 80 of 87, dementia preceded HF. A combination of low coronary artery calcium score and low high-sensitivity cardiac troponin T was significantly associated with reduced risk of dementia and HF. CONCLUSIONS: Most participants with HF had dementia but with onset before HF. Lower high-sensitivity cardiac troponin T and coronary artery calcium was associated with low risk of dementia based on a small number of events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.
Asunto(s)
Envejecimiento , Aterosclerosis/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Demencia/epidemiología , Insuficiencia Cardíaca/epidemiología , Corazón/fisiopatología , Enfermedades Renales/epidemiología , Riñón/fisiopatología , Calcificación Vascular/epidemiología , Factores de Edad , Anciano de 80 o más Años , Enfermedades Asintomáticas , Aterosclerosis/diagnóstico , Aterosclerosis/mortalidad , Aterosclerosis/fisiopatología , Biomarcadores/sangre , Causas de Muerte , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Cistatina C/sangre , Demencia/diagnóstico , Demencia/mortalidad , Demencia/fisiopatología , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Incidencia , Enfermedades Renales/diagnóstico , Enfermedades Renales/mortalidad , Enfermedades Renales/fisiopatología , Imagen por Resonancia Magnética , Masculino , Péptido Natriurético Encefálico/sangre , Pruebas Neuropsicológicas , Pennsylvania/epidemiología , Fragmentos de Péptidos/sangre , Prevalencia , Factores de Riesgo , Factores de Tiempo , Troponina T/sangre , Calcificación Vascular/diagnóstico , Calcificación Vascular/mortalidad , Calcificación Vascular/fisiopatologíaRESUMEN
INTRODUCTION: The association between history of coronary artery bypass graft surgery (CABG) and dementia risk remains unclear. METHODS: We conducted a prospective cohort analysis using data on 3155 elderly adults free from prevalent dementia from the US population-based Cardiovascular Health Study (CHS) with adjudicated incident all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia. RESULTS: In the CHS, the hazard ratio (HR) for all-cause dementia was 1.93 [95% confidence interval (CI), 1.36-2.74] for those with CABG history compared with those with no CABG history after adjustment for potential confounders. Similar HRs were observed for AD (HR=1.71; 95% CI, 0.98-2.98), VaD (HR=1.42; 95% CI, 0.56-3.65), and mixed dementia (HR=2.73; 95% CI, 1.55-4.80). The same pattern of results was observed when these CHS findings were pooled with a prior prospective study, the pooled HRs were 1.96 (95% CI, 1.42-2.69) for all-cause dementia, 1.71 (95% CI, 1.04-2.79) for AD and 2.20 (95% CI, 0.78-6.19) for VaD. DISCUSSION: Our results suggest CABG history is associated with long-term dementia risk. Further investigation is warranted to examine the causal mechanisms which may explain this relationship or whether the association reflects differences in coronary artery disease severity.
Asunto(s)
Puente de Arteria Coronaria/efectos adversos , Demencia/epidemiología , Anciano , Enfermedades Cardiovasculares/complicaciones , Femenino , Humanos , Masculino , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Estados UnidosRESUMEN
PURPOSE: Wrist-worn accelerometer devices measure sleep in free-living settings. Few studies, however, have investigated whether these devices can also measure waking movement behavior (e.g., total movement volume, physical activity). The purpose of this study was to investigate the ability of a wrist-worn Actiwatch 2 sleep monitor to rank total movement volume and physical activity levels compared with a waist-worn ActiGraph GT1M accelerometer and self-reported leisure time physical activity, respectively. In addition, we compared temporally matched activity measured via the ActiGraph GT1M and Actiwatch 2 over the study week. METHODS: A subset of women from the Healthy Women Study (n = 145; age, 73.3 ± 1.7 yr) wore an Actiwatch 2 on their nondominant wrist and an ActiGraph GT1M on their dominant hip for seven consecutive days. Participants recorded their leisure time physical activity in a 7-d diary and completed the past year version of the Modifiable Activity Questionnaire. Analyses were conducted for all wake periods and separately for active periods when both devices were worn. RESULTS: Spearman rank-order correlation coefficients for total movement volume between the Actiwatch 2 and ActiGraph GT1M were significant for wake periods (r = 0.47, P < 0.001) and, to a lesser extent, for active periods (r = 0.26, P < 0.01). However, the Actiwatch 2 did not rank participant's physical activity levels similarly to self-reported leisure time physical activity estimates (κ ≤ 0.05, P > 0.05). Multilevel model analyses comparing temporally matched activity measured via the ActiGraph GT1M and Actiwatch 2 suggest that the two devices yielded similar levels of activity during wake periods (B = 0.90; SE, 0.008; P < 0.001) and during active periods (B = 0.81; SE, 0.01; P < 0.001). CONCLUSIONS: A wrist-worn Actiwatch 2 may be useful for ranking total movement volume and for assessing the pattern of activity over a day in older women. However, our data do not support using a wrist-worn Actiwatch 2 device for measuring physical activity.
Asunto(s)
Actigrafía/instrumentación , Actividad Motora/fisiología , Actividades Cotidianas , Anciano , Femenino , Humanos , Actividades Recreativas , Sueño , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. METHODS: We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. RESULTS: In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. CONCLUSIONS: The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.
Asunto(s)
Calcinosis/sangre , Enfermedad de la Arteria Coronaria/sangre , Osteoprotegerina/sangre , Posmenopausia/sangre , Ligando RANK/sangre , Receptor Activador del Factor Nuclear kappa-B/sangre , Triglicéridos/sangre , Biomarcadores/sangre , Calcinosis/fisiopatología , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
PURPOSE: The objective of this study is to examine the temporal and bidirectional relationships between accelerometer-derived physical activity estimates and actigraphy-assessed sleep characteristics among older women. METHODS: A subgroup of participants (N = 143, mean age = 73 yr) enrolled in the Healthy Women Study wore an ActiGraph accelerometer on their waist and an Actiwatch sleep monitor on their wrist concurrently for seven consecutive days. Multilevel models examined whether ActiGraph-assessed daily activity counts (ct·min⻹·d⻹) and moderate- to vigorous-intensity physical activity (MVPA; min·d⻹) predicted Actiwatch-assessed sleep onset latency, total sleep time, sleep efficiency, and sleep fragmentation. Similar models were used to determine whether nighttime sleep characteristics predicted physical activity the following day. RESULTS: In unadjusted models, greater daily activity counts (B = -0.05, P = 0.005) and more minutes of MVPA (B = -0.03, P = 0.01) were temporally associated with less total sleep time across the week. Greater sleep efficiency was associated with greater daily activity counts (B = 0.37, P = 0.01) and more minutes of MVPA (B = 0.64, P = 0.009) the following day. Less sleep fragmentation was also associated with greater daily activity counts and more MVPA the following day. Findings were similar after adjustment for age, education, body mass index, depressive symptoms, arthritis, and accelerometer wear time. CONCLUSIONS: Few studies have used objective measures to examine the temporal relationships between physical activity and sleep. Notably, these findings suggest that nightly variations in sleep efficiency influence physical activity the following day. Thus, improving overall sleep quality in addition to reducing nightly fluctuations in sleep may be important for encouraging a physically active lifestyle in older women.
Asunto(s)
Actigrafía , Actividad Motora/fisiología , Sueño , Actigrafía/instrumentación , Anciano , Estudios Transversales , Femenino , Humanos , Estilo de Vida , Esfuerzo Físico/fisiología , Salud de la MujerRESUMEN
Vitamin D deficiency is highly prevalent worldwide, and is linked to several major chronic, inflammatory and autoimmune diseases. Vitamin D deficiency has not been evaluated in dark skinned individuals living in areas of high sun exposure utilizing more reliable mass spectrometry assay techniques. We determined the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in Afro-Caribbean men on the tropical island of Tobago, where there is a high level of sunshine year round. Serum 25(OH)D2 and 25(OH)D3 metabolites were measured following extraction and purification using liquid chromatography and tandem mass spectrometry in 424 Afro-Caribbean men aged > 65 years from a larger population-based cohort study. The mean (+/- SD) serum total 25(OH)D concentration was 35.1 +/- 8.9 ng/mL. Deficiency (< 20 ng/mL) was present in only 2.8% and insufficiency (< 30 ng/mL) in 24% of the men. Multiple linear regression analysis identified age, BMI and daily vitamin D supplementation as the independent correlates of 25(OH)D. None of the men who consumed fish more than once per week had vitamin D deficiency, compared to 4% of the men who consumed fish once per week or less (P = .01, adjusted for age, BMI, and daily vitamin D supplementation). In conclusion, vitamin D deficiency is very uncommon in this Afro-Caribbean population. Longitudinal studies are needed to delineate the possible effects of high vitamin D levels in this population on major diseases hypothesized to be associated with vitamin D deficiency.
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Población Negra , Deficiencia de Vitamina D/etnología , Anciano , Anciano de 80 o más Años , Humanos , Modelos Lineales , Masculino , Análisis Multivariante , Prevalencia , Trinidad y Tobago/epidemiología , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
UNLABELLED: Abstract Background: Skeletal muscle adipose tissue (AT) infiltration, or myosteatosis, appears to be greater in African compared with European ancestry individuals and may play a role in type 2 diabetes mellitus (T2DM), a disease that disproportionally affects African ancestry populations. Inflammation is one mechanism that may link myosteatosis with increased T2DM risk, but studies examining the relationship between inflammation and myosteatosis are lacking. METHODS: To examine these associations, we measured skeletal muscle subcutaneous AT, intermuscular AT, and skeletal muscle density using quantitative computed tomography and serum markers of inflammation in 471 individuals from 8 Afro-Caribbean multigenerational families [mean family size 67; mean age 43 years; mean body mass index (BMI) 28 kg/m(2)]. RESULTS: After removing the variation attributable to significant covariates, heritabilities of inflammation markers [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] ranged from 33% (TNFα) to 40% (CRP); all P<0.01. Higher CRP, IL-6, and TNF-α were associated with lower subcutaneous AT around skeletal muscle (r=-0.13 to -0.19, P<0.05). Higher CRP was additionally associated with lower skeletal muscle density, indicative of greater intramuscular AT (r=-0.10, P<0.05), hyperinsulinemia (r=0.12, P<0.05), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.17, P<0.01). CONCLUSIONS: Our findings suggest that heredity may play a significant role in the determination of several markers of inflammation in African ancestry individuals. Higher concentrations of CRP appear to be associated with greater skeletal muscle AT infiltration, lower subcutaneous AT, hyperinsulinemia, and insulin resistance. Longitudinal studies are needed to further evaluate the relationship between inflammation with changes in skeletal muscle AT distribution with aging and the incidence of T2DM.
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Adiposidad/genética , Población Negra/genética , Mediadores de Inflamación/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Coristoma/patología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/genética , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Músculo Esquelético/anatomía & histología , Factores de Riesgo , Grasa Subcutánea/anatomía & histología , Trinidad y Tobago , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry; and calf skeletal muscle fat distribution (subcutaneous and intermuscular fat; skeletal muscle density) was measured using quantitative computed tomography in 472 Afro-Caribbean men 65 years and older. Bioactive androgens, testosterone, free testosterone, and dihydrotestosterone were associated with less skeletal muscle fat infiltration (r = -0.14 to -0.18, P < .05) and increased skeletal muscle density (r = 0.10 to 0.14, P < .05), independent of total adiposity. In addition, glucuronidated androgen metabolites were associated with less subcutaneous fat (r = -0.11 to -0.15, P < .05). Multivariate logistic regression analysis identified an increased level of 3α-diol-3 glucuronide (odds ratio = 1.38, P < .01) and a decreased level of dihydrotestosterone (odds ratio = 0.66, P < .01) to be significantly associated with T2DM. Our findings suggest that, in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM.
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Adiposidad/fisiología , Envejecimiento/metabolismo , Andrógenos/metabolismo , Músculo Esquelético/metabolismo , Anciano , Anciano de 80 o más Años , Población Negra , Composición Corporal/fisiología , Índice de Masa Corporal , Humanos , Resistencia a la Insulina/fisiología , Masculino , Sobrepeso/metabolismo , Trinidad y TobagoRESUMEN
Skeletal muscle fat is greater in African ancestry individuals compared with whites, is associated with diabetes, and is a heritable polygenic trait. However, specific genetic factors contributing to skeletal muscle fat in humans remain to be defined. Muscle carnitine palmitoyltransferase-1B (CPT1B) is a key enzyme in the regulation of skeletal muscle mitochondrial beta-oxidation of long-chain fatty acids, and as such is a reasonable biological candidate gene for skeletal muscle fat accumulation. Therefore, we examined the association of three nonsynonymous coding variants in CPT1B (G531L, I66V, and S427C; a fourth, A320G, could not be genotyped) and quantitative computed tomography measured tibia skeletal muscle composition and BMI among 1,774 Afro-Caribbean men aged > or =40, participants of the population-based Tobago Health Study. For all variants, no significant differences were observed for BMI or total adipose tissue. Among individuals who were homozygous for the minor allele at G531L or I66V, intermuscular adipose tissue (IMAT) was 87% (P = 0.03) and 54% lower (P = 0.03), respectively. In contrast, subcutaneous adipose tissue (SAT) was 11% (P = 0.017) and 7% (P = 0.049) higher, respectively, than among individuals without these genotypes. These associations were independent of age, body size, and muscle area. Finally, no individuals with type 2 diabetes were found among those who were homozygous for the minor allele of either at G531L and I66V whereas 14-18% of men with the major alleles had type 2 diabetes (P = 0.03 and 0.007, respectively). Our results suggest a novel association between common nonsynonymous coding variants in CPT1B and ectopic skeletal muscle fat among middle-aged and older African ancestry men.
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Adiposidad/genética , Adiposidad/fisiología , Población Negra/genética , Distribución de la Grasa Corporal , Carnitina O-Palmitoiltransferasa/genética , Músculo Esquelético/fisiopatología , Adiposidad/etnología , Anciano , Alelos , Población Negra/etnología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Grasa Subcutánea/fisiopatología , Trinidad y TobagoRESUMEN
BACKGROUND: Although obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. OBJECTIVE: We examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged >or=40 y. DESIGN: Anthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). RESULTS: The prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/m(2)) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). CONCLUSIONS: These findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.'
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Tejido Adiposo/crecimiento & desarrollo , Tejido Adiposo/fisiología , Envejecimiento/fisiología , Población Negra , Diabetes Mellitus/epidemiología , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/fisiología , Adulto , Anciano , Población Negra/estadística & datos numéricos , Glucemia/análisis , Índice de Masa Corporal , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Trinidad y TobagoRESUMEN
BACKGROUND: Although obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. OBJECTIVE: We examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged >or=40 y. DESIGN: Anthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). RESULTS: The prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/m(2)) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). CONCLUSIONS: These findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.'
Asunto(s)
Adulto , Persona de Mediana Edad , Anciano , Humanos , Masculino , Tejido Adiposo/crecimiento & desarrollo , Tejido Adiposo/fisiología , Población Negra/estadística & datos numéricos , Envejecimiento/fisiología , Glucemia/análisis , Índice de Masa Corporal , Diabetes Mellitus/epidemiología , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/fisiología , Análisis de Regresión , Trinidad y TobagoRESUMEN
BACKGROUND: Afro-Caribbeans from Tobago are at high risk of developing prostate cancer. This elevated risk of prostate cancer is shared by populations of African ancestry living in diverse environments in the Western hemisphere. Variation in the ribonuclease L (RNASEL) gene has recently been reported to be associated with an increased risk of prostate cancer. However, whether RNASEL variation contributes to the increased risk of prostate cancer observed in populations of African ancestry remains unclear. METHODS: We resequenced the positional candidate gene RNASEL in 48 prostate cancer cases and genotyped the previously reported R462Q and D541E polymorphisms in 230 prostate cancer cases and 458 controls. We also examined the inhibitor of RNASEL (ABCE1) for variation associated with prostate cancer risk. RESULTS: We found no evidence of association between R462Q and D541E polymorphisms and prostate cancer risk in our case/control analysis. A novel variant (K294E) was identified in a single heterozygous individual with prostate cancer. We also observed a 20 bp insertion/deletion polymorphism 1,109 bp upstream of the initiation codon, but this variant was not associated with prostate cancer. We identified 16 single nucleotide polymorphisms in the ABCE1 gene, only 3 of which had a minor allele frequency >5%. A common A/G transition -1,071 bp from the transcriptional start site was genotyped and showed no evidence of association with prostate cancer. CONCLUSIONS: Our results suggest that common variation in the putative prostate cancer susceptibility gene, RNASEL, or its inhibitor does not contribute significantly to prostate cancer risk in this Afro-Caribbean population.
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Transportadoras de Casetes de Unión a ATP/genética , Chaperoninas/genética , Endorribonucleasas/genética , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/genética , Adulto , Anciano , Población Negra/estadística & datos numéricos , Cromosomas Humanos Par 4 , Ligamiento Genético , Predisposición Genética a la Enfermedad/etnología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Prevalencia , Factores de Riesgo , Trinidad y Tobago/epidemiologíaRESUMEN
Adiponectin, an adipose-specific protein, is negatively associated with adiposity, insulin sensitivity, and diabetes. Very few studies have examined the role of heredity in the regulation of adiponectin and its association with body fat among individuals of African heritage. Thus, we measured fasting serum adiponectin levels by radioimmunoassay and body composition by dual-energy x-ray absorptiometry (DEXA) in 402 individuals aged 18 to 103 years belonging to 7 multigenerational families of African heritage in the relatively homogeneous island population of Tobago. Heritability of adiponectin was 33.2% (P < .01), and age, sex, and body mass index explained 23.4% of the variance in adiponectin. Sex-specific heritability was significant in men (heritability, 34%; P < .05), but not in women. The inverse associations between body mass index and percentage of body fat and adiponectin, independent of age and height, were much stronger in women (all P values <.001) than in men. However, percentage of trunk fat was consistently strongly associated with adiponectin in both men (r = -0.40, P < .001) and women (r = -0.44, P < .001), independent of age and height. This study suggests that genetic factors are a significant source of interindividual differences in circulating adiponectin among Afro-Caribbeans. Adiponectin may serve as a promising quantitative intermediate trait in studies designed to map the genes underlying diabetes and obesity in this population.
Asunto(s)
Adiponectina/genética , Adiponectina/fisiología , Tejido Adiposo/fisiología , Adiposidad/genética , Adiposidad/fisiología , Absorciometría de Fotón , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antropometría , Población Negra , Composición Corporal , Índice de Masa Corporal , Ambiente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Trinidad y TobagoRESUMEN
OBJECTIVE: To test the hypothesis that bone mineral density (BMD), a possible surrogate of lifetime exposure to hormone/growth factor/vitamin D/calcium exposure, is higher in prostate cancer cases than controls. METHODS: Hip BMD was measured by dual X-ray absorptiometry in 222 Afro-Caribbean screening-detected prostate cancer cases and 1,503 screened non-cases, aged 45-79, in the population-based Tobago Prostate Survey. Because possible skeletal metastases may modulate BMD, men with prostate specific antigen >20 ng/ml or highly undifferentiated tumors (Gleason score > or = 8) were excluded. Mean BMD, adjusted for age and body mass index, was compared in cases and non-cases by analysis of variance. Risk across age group-specific BMD quartiles was compared using logistic regression. RESULTS: Overall, adjusted mean hip BMD was higher in cases (1.157 g/cm2) than non-cases (1.134 g/cm2) (p = 0.02). In men aged 60-79, prostate cancer risk was two-fold higher (OR, 2.12; 95% CI: 1.21-3.71) in the highest BMD quartile compared to the lowest. There was no association in younger men (interaction, p = 0.055). CONCLUSIONS: High bone density is associated with prostate cancer among older men, consistent with an etiological role for lifetime exposure to factors which modulate bone density. However, other etiologies may dominate prostate cancer risk among younger men.
Asunto(s)
Envejecimiento/fisiología , Población Negra/estadística & datos numéricos , Densidad Ósea/fisiología , Encuestas Epidemiológicas , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/fisiopatología , Adulto , Distribución por Edad , Anciano , Estudios de Casos y Controles , Cadera/fisiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Trinidad y Tobago/epidemiologíaRESUMEN
Despite a higher prevalence of coronary heart disease risk factors, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than whites. In part, this is thought to be because of the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower triglycerides and higher high-density lipoprotein (HDL) cholesterol. We hypothesized that the -514C>T polymorphism in the hepatic lipase gene (LIPC) plays a significant role in determining a less atherogenic lipoprotein profile observed in men of African origin. Previously conducted studies of the LIPC -514C>T polymorphism in African Americans may have been confounded by a higher level of European admixture; in addition, the results from these studies do not necessarily apply to other African populations because gene-environment interactions may differ. Thus, we compared nuclear magnetic resonance spectroscopy-measured lipoprotein subclass patterns and LIPC -514C>T genotypes in population-based samples of older white American (n = 532) and African American (n = 97) men from the Cardiovascular Health Study to those among older, less admixed, Afro-Caribbean men (n = 205) from the Tobago Health Study. Men of African origin had a more favorable lipoprotein profile than whites. In addition, levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride, and large and small very low-density lipoprotein, small low-density lipoprotein, as well as very low-density lipoprotein particle size, were remarkably lower in Afro-Caribbean men than in either African American or white men. The frequency of the LIPC -514T allele was much higher in Afro-Caribbeans (0.57) and in African Americans (0.49) than in whites (0.20). The -514T allele in both populations of African origin, but not in whites, was associated with elevated large HDL and greater HDL size. Our findings indicate that the higher frequency of the LIPC -514T allele found in men of African origin living in different environments significantly contributes to the more favorable distribution of HDL subclasses compared with whites.
Asunto(s)
Lipasa/genética , Lipoproteínas/sangre , Hígado/enzimología , Adulto , Negro o Afroamericano , Factores de Edad , Anciano , Alelos , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Región del Caribe , Estudios de Cohortes , ADN/genética , Frecuencia de los Genes , Variación Genética , Humanos , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Trinidad y Tobago/epidemiología , Estados Unidos/epidemiología , Población BlancaRESUMEN
To test the hypothesis that variation in the putative prostate cancer susceptibility gene ELAC2 contributes to the elevated risk of prostate cancer in Afro-Caribbean males from Tobago, we genotyped the S217L and A514T polymorphisms, previously reported to be associated with prostate cancer risk in a large sample of cases and controls. The frequency of the high-risk Leu allele at the S217L site was the same in cases and controls. Both cases and controls were homozygous for the low-risk Ala allele at the A514T site. In addition, we sequenced the exons and 3'- and 5'-flanking regions of ELAC2 in 24 individuals with histologically confirmed prostate cancer. We identified 17 new single nucleotide polymorphisms. An A(-1196)T polymorphism, which alters a predicted TATA box consensus sequence, was tested in cases and controls, and no significant difference in allele or genotype frequencies was observed. The absence of ELAC2 mutations and lack of association between polymorphisms in ELAC2 and prostate cancer in cases and controls leads us to conclude that ELAC2 does not contribute significantly to the elevated prevalence of prostate cancer in Afro-Caribbean males of Tobago.