Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 364
Filtrar
1.
BMJ Open ; 9(7): e029716, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350252

RESUMO

INTRODUCTION: Prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association. METHODS AND ANALYSIS: We will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal. PROSPERO REGISTRATION NUMBER: CRD42018091627.

2.
Aging Ment Health ; : 1-9, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31184203

RESUMO

Objectives: We investigated if perceived stress in midlife increased the risk of dementia. Furthermore, we explored differences between subgroups related to sex, age and employment status when reporting stress. Methods: In this longitudinal study, we used information on perceived stress from 10,814 participants (mean age 56.7 years). Participants were followed through Danish national registers for development of dementia. Participants were considered at risk of dementia from the date they turned 60 years. Perceived stress was assessed as a combination of self-reported intensity and frequency of stress, and categorized into low (score 0-1), medium (score 2-4), and high stress (score 5-6). We used Poisson regression to estimate incidence rate ratios (IRR) and their 95% confidence intervals (CI) and adjusted for sociodemographic factors and psychiatric morbidity at baseline (main model) as well as cardio/cerebrovascular diseases and health behaviors at baseline (additional model). Results: The mean follow-up time was 13.8 years, and 1,519 participants were registered with dementia. Dementia risk was higher in participants reporting medium stress (IRR = 1.11, 95% CI: 0.99-1.24) and high stress (IRR = 1.36, 95% CI: 1.13-1.65). Adjustment for cardio/cerebrovascular diseases and health behaviors did not alter the results. We did not find strong support for differences between subgroups, although the association between stress and dementia was stronger for those who were employed at the time of reporting high stress. Conclusion: Our results provide empirical support for an effect of perceived stress on the risk of dementia in old age.

3.
J Innate Immun ; : 1-12, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31230049

RESUMO

The incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune responsiveness. The aim of the present study was to investigate sex differences in monocyte-derived cytokine production response upon stimulation with the gram-negative stimulus lipopolysaccharide (LPS) using cytokine data from 15 study populations. Individual data on ex vivo cytokine production response upon stimulation with LPS in whole blood were available for 4,020 subjects originating from these 15 study populations, either from the general population or from patient populations with specific diseases. Men had a stronger cytokine production response than women to LPS for tumour necrosis factor-α, interleukin (IL)-6, IL-12, IL-1ß, IL-1RA, and IL-10, but not for interferon-γ. The granulocyte-macrophage colony-stimulating factor production response was lower in men than in women. These sex differences were independent of chronological age. As men had higher monocyte concentrations, we normalized the cytokine production responses for monocyte concentration. After normalization, the sex differences in cytokine production response to LPS disappeared, except for IL-10, for which the production response was lower in men than in women. A sex-based approach to interpreting immune responsiveness is crucial.

4.
Aging Cell ; 18(4): e12956, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31062498

RESUMO

With advancing age, many organs exhibit functional deterioration. The age-associated accumulation of senescent cells is believed to represent one factor contributing to this phenomenon. While senescent cells are found in several different organ systems, it is not known whether they arise independently in each organ system or whether their prevalence within an individual reflects that individual's intrinsic aging process. To address this question, we studied senescence in two different organ systems in humans, namely skin and T cells in 80 middle-aged and older individuals from the Leiden Longevity Study. Epidermal p16INK4a positivity was associated with neither CD4+ nor CD8+ T-cell immunosenescence phenotype composites (i.e., end-stage differentiated/senescent T cells, including CD45RA+ CCR7- CD28- CD27- CD57+ KLRG1+ T cells). Dermal p16INK4a positivity was significantly associated with the CD4+ , but not with the CD8+ immunosenescence composite. We therefore conclude that there is limited evidence for a link between skin senescence and immunosenescence within individuals.

5.
BMJ Open ; 9(5): e027027, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31129586

RESUMO

OBJECTIVE: Shift work and long working hours are potential risk factors for dementia, but previous studies on shift work, long working hours and dementia are sparse and their findings are conflicting. Therefore, we investigated the effect of night shift work and long working hours on dementia. DESIGN: A longitudinal study. SETTING: Denmark. PARTICIPANTS: 3435 occupationally active men and women from the general working population. METHODS: Work schedule covered day work (reference) and shift schedules without/with night work. Working hours covered <27, 28-36, 37 (reference), 38-44, and ≥45 hours/week. As the primary outcome, we used register-based information about dementia, and estimated incidence rate ratios (IRR) and 95% CI. Estimates were adjusted for gender, age, psychosocial work factors and cardiovascular risk factors. RESULTS: We identified 85 dementia cases during a mean of 9.8 years of follow-up. We found a positive, but statistically insignificant association between night shift work and dementia (IRR=2.01; 95% CI: 0.87-4.65). Post hoc analyses indicated that this was only due to a higher risk in permanent night workers (IRR=3.25; 95% CI: 1.35-7.83). The dementia risk was also significantly higher among participants working 38-44 hours/week (IRR=2.08; 95% CI: 1.11-3.90) compared with those working 37 hours/week. We found no indications of a higher risk of dementia in participants working <37 hours/week or ≥45 hours/week. CONCLUSION: We did not find arguments that night shift work or long working hours increased dementia risk in general. However, we found a higher risk of dementia in specific subgroups, that is, permanent night workers and employees with moderately longer weekly working hours than the standard.

6.
J Clin Endocrinol Metab ; 103(10): 3658-3667, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113667

RESUMO

Context: Anemia and thyroid dysfunction often co-occur, and both increase with age. Human data on relationships between thyroid disease and anemia are scarce. Objective: To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia. Design: Individual participant data meta-analysis. Setting: Sixteen cohorts participating in the Thyroid Studies Collaboration (n = 42,162). Main Outcome Measures: Primary outcome measure was anemia (hemoglobin <130 g/L in men and <120 g/L in women). Results: Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants [overt hypothyroidism, pooled OR 1.84 (95% CI 1.35 to 2.50), subclinical hypothyroidism 1.21 (1.02 to 1.43), subclinical hyperthyroidism 1.27 (1.03 to 1.57), and overt hyperthyroidism 1.69 (1.00 to 2.87)]. Hemoglobin levels were lower in all groups compared with participants with euthyroidism. In the longitudinal analyses (n = 25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 (95% CI 0.86 to 2.20) for overt hypothyroidism, 1.18 (1.00 to 1.38) for subclinical hypothyroidism, 1.15 (0.94 to 1.42) for subclinical hyperthyroidism, and 1.47 (0.91 to 2.38) for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups. Conclusion: Higher odds of having anemia were observed in participants with both hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.

7.
Eur J Intern Med ; 57: 7-18, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30017559

RESUMO

BACKGROUND: Numerous risk prediction models use indicators of health to predict mortality in old age. The added value to mortality predictions based on demographic variables is unknown. OBJECTIVE: To evaluate the accuracy of health indicators in predicting all-cause mortality among individuals aged 50+ using area under receiver operating characteristic curve (AUC). Specifically, to assess the added value of health indicators relative to demographic variables. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. There were no restrictions on study designs, follow-up duration, language, or publication dates. We also examined the quality of studies using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies. RESULTS: Out of 804 studies investigating all-cause mortality in older persons, 16 studies were eligible. In community-dwelling populations, the accuracy of demographic variables and health indicators combined ranged from AUC 0.71 to 0.82, indicating modest ability to predict mortality. Age contributed the most to mortality prediction (AUC 0.65 to 0.78) and compared to age and sex, the added values of genetics, physiology, functioning, mood, cognition, nutritional status, subjective health, disease, frailty, and lifestyle ranged from AUC 0.01 to 0.10. The lack of validation samples made it difficult to assess their true added value. Findings were similar in institutionalized populations. Heterogeneity of the studies prevented us from performing a meta-analysis. CONCLUSION: Age and sex contributed the most to mortality predictions in old age while the added value of health indicators is likely to be limited.

8.
Aging (Albany NY) ; 10(2): 278-289, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29500330

RESUMO

Little is known on how well senescence markers in vitro and in situ correlate within individual donors. We studied correlations between the same and different in vitro markers. Furthermore, we tested correlations between in vitro markers with in situ p16INK4a positivity.From 100 donors (20-91 years), cultured dermal fibroblasts were assessed for reactive oxygen species (ROS), telomere-associated foci (TAF), p16INK4a and senescence-associated ß-gal (SAß-gal), with/ without 0.6 µM rotenone for 3 days (short-term). In fibroblasts from 40 donors, telomere shortening, ROS and SAß-gal were additionally assessed, with/ without 20 nM rotenone for 7 weeks (long-term). In skin from 52 donors, the number of p16INK4a positive dermal cells was assessed in situ.More than half of the correlations of the same senescence markers in vitro between duplicate experiments and between short-term versus long-term experiments were significant. Half of the different senescence marker correlations were significant within the short-term and within the long-term experiments. The different senescence markers in vitro were not significantly correlated intra-individually with in situ p16INK4a positivity.In conclusion, the same and different senescence markers are frequently correlated significantly within and between in vitro experiments, but in vitro senescence markers are not correlated with p16INK4a positivity in situ.

9.
J Hypertens ; 36(4): 773-778, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29189468

RESUMO

BACKGROUND: In older age, a low DBP has been associated with increased risk of cardiovascular events, especially in frail older people. We tested the hypothesis that low DBP is associated with a high risk of cardiovascular events in people with a previous history of cardiovascular disease, as a proxy of vascular impairment. METHODS: We included 5804 participants (mean age 75 years) from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) who as part of the trial were intensively monitored for an average period of 3.2 years. DBP was categorized in low (<70 mmHg), normal (70-90 mmHg) or high (>90 mmHg). Cox proportional hazards analyses were used to estimate hazard ratio with 95% confidence intervals (CI); analyses were stratified for cardiovascular history. RESULTS: Participants with low DBP had a 1.24-fold (1.04; 1.49) increased risk of cardiovascular events compared with those with normal DBP. After further adjusting for cardiovascular factors, this association attenuated to 1.05 (0.86; 1.28). A previous history of cardiovascular disease significantly modified the relation between DBP and risk of cardiovascular events (P-interaction 0.042). In participants without a history of cardiovascular disease, DBP was marginally significantly associated with an increased event risk (hazard ratio (95% CI) per 10 mmHg increase in DBP 1.08 (0.99; 1.18), P value = 0.07), whereas in participants with a history of cardiovascular disease, higher DBP was associated with a decreased risk of cardiovascular events (hazard ratio (95% CI) per 10 mmHg increase in DBP 0.92 (0.85; 0.99, P value = 0.018). These risk estimates were independent of potential confounders, including classical cardiovascular risk factors. CONCLUSION: The association of DBP with cardiovascular events in older people varies upon their previous history, showing that in participants with preexisting cardiovascular diseases, a higher DBP associates with a decreased risk of future cardiovascular events.

11.
Circulation ; 136(22): 2100-2116, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29061566

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. METHODS: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. RESULTS: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. CONCLUSIONS: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.


Assuntos
Fibrilação Atrial/epidemiologia , Hipotireoidismo/epidemiologia , Glândula Tireoide/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Testes de Função Tireóidea , Glândula Tireoide/metabolismo , Tireotropina/sangue , Tiroxina/sangue , Fatores de Tempo , Adulto Jovem
12.
Aging (Albany NY) ; 9(10): 2223-2234, 2017 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-29070732

RESUMO

The relationship between thyroid status and longevity has been investigated extensively. However, data on thyroid status and survival in old age is scarce. In this study we investigated associations of different parameters of thyroid status with mortality in nonagenarians, and whether these associations were different in nonagenarians from long-lived families than in nonagenarians from the general population. In total, 805 nonagenarians from the Leiden Longevity Study and 259 nonagenarians from the Leiden 85-plus Study were followed up to collect mortality data. At baseline, levels of thyrotropin (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured. In nonagenarians from long-lived families and from the general population, associations between thyroid parameters and mortality were similar. We found no interaction between study population and parameters of thyroid status on mortality (P-values>0.70). The results from both studies were combined to derive generalizable associations. Hazard ratios (HRs) for the highest compared to lowest tertiles were determined, resulting in TSH HR 0.91 (P=0.25), fT4 HR 1.22 (P=0.02), fT3 HR 0.74 (P=1.31e-4), and fT3/fT4 HR 0.66 (P=5.64e-7). In conclusion, higher fT3/fT4 ratios, higher levels of fT3, and lower levels of fT4 were associated with lower mortality rate in nonagenarians and independent of familial longevity status.


Assuntos
Longevidade/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Glândula Tireoide
13.
Cleve Clin J Med ; 84(9): 699-700, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28885901
14.
PLoS One ; 12(7): e0179497, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28683096

RESUMO

BACKGROUND: The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility. METHODS AND FINDINGS: This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018). CONCLUSIONS: Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.


Assuntos
Apolipoproteína E4/imunologia , Doenças Transmissíveis/imunologia , Fertilidade/imunologia , Paridade/imunologia , Adulto , Idoso , Alelos , Apolipoproteína E4/genética , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/genética , Doenças Transmissíveis/mortalidade , Água Potável/microbiologia , Água Potável/parasitologia , Água Potável/virologia , Feminino , Expressão Gênica , Frequência do Gene , Gana/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , População Rural , Classe Social , Análise de Sobrevida
15.
Eur J Intern Med ; 42: 29-38, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28583408

RESUMO

OBJECTIVE: To investigate the added value of comorbidity, frailty, and subjective health to mortality predictions in community-dwelling older people and whether it changes with increasing age. PARTICIPANTS: 36,751 community-dwelling subjects aged 50-100 from the longitudinal Survey of Health, Ageing, and Retirement in Europe. METHODS: Mortality risk associated with Comorbidity Index, Frailty Index, Frailty Phenotype, and subjective health was analysed using Cox regression. The extent to which health indicators modified individual mortality risk predictions was examined and the added ability to discriminate mortality risks was assessed. MAIN OUTCOME MEASURES: Three-year mortality risks, hazard ratios, change in individual mortality risks, three-year area under the receiver operating characteristic curve (AUC). RESULTS: Three-year mortality risks increased 41-folds within an age span of 50years. Hazard ratios per change in health indicator became less significant with increasing age (p-value<0·001). AUC for three-year mortality prediction based on age and sex was 76·9% (95% CI 75·5% to 78·3%). Information on health indicators modified individual three-year mortality risk predictions up to 30%, both upwards and downwards, each adding <2% discriminative power. The added discrimination ability of all health indicators gradually declined from an extra 4% at age 50-59 to <1% in the oldest old. Trends were similar for one-year mortality and not different between sexes, levels of education, and household income. CONCLUSION: Calendar age encompasses most of the discrimination ability to predict mortality. The added value of comorbidity, frailty, and subjective health to mortality predictions decreases with increasing age.


Assuntos
Comorbidade/tendências , Autoavaliação Diagnóstica , Idoso Fragilizado/estatística & dados numéricos , Mortalidade/tendências , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Europa (Continente)/epidemiologia , Feminino , Indicadores Básicos de Saúde , Humanos , Vida Independente , Cooperação Internacional , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Medição de Risco , Distribuição por Sexo , Análise de Sobrevida
16.
Nature ; 546(7660): E11-E12, 2017 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-28658235
17.
J Clin Endocrinol Metab ; 102(8): 2719-2728, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28482002

RESUMO

Context: Hyperthyroidism is associated with increased fracture risk, but it is not clear if lower thyroid-stimulating hormone (TSH) and higher free thyroxine (FT4) in euthyroid individuals are associated with fracture risk. Objective: To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals. Design: Individual participant data analysis. Setting: Thirteen prospective cohort studies with baseline examinations between 1981 and 2002. Participants: Adults with baseline TSH 0.45 to 4.49 mIU/L. Main Outcome Measures: Primary outcome was incident hip fracture. Secondary outcomes were any, nonvertebral, and vertebral fractures. Results were presented as hazard ratios (HRs) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45 to 0.99 mIU/L; 1.00 to 1.49 mIU/L; 1.50 to 2.49 mIU/L; 2.50 to 3.49 mIU/L; and 3.50 to 4.49 mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results: During 659,059 person-years, 2,565 out of 56,835 participants had hip fracture (4.5%; 12 studies with data on hip fracture). The pooled adjusted HR (95% CI) for hip fracture was 1.25 (1.05 to 1.49) for TSH 0.45 to 0.99 mIU/L, 1.19 (1.01 to 1.41) for TSH 1.00 to 1.49 mIU/L, 1.09 (0.93 to 1.28) for TSH 1.50 to 2.49 mIU/L, and 1.12 (0.94 to 1.33) for TSH 2.50 to 3.49 mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 [HR (95% CI) 1.22 (1.11 to 1.35) per one standard deviation increase in FT4]. FT4 only was associated with any and nonvertebral fractures. Results remained similar in sensitivity analyses. Conclusions: Among euthyroid adults, lower TSH and higher FT4 are associated with an increased risk of hip fracture. These findings may help refine the definition of optimal ranges of thyroid function tests.


Assuntos
Fraturas do Quadril/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Tireotropina/sangue , Tiroxina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
18.
N Engl J Med ; 376(26): 2534-2544, 2017 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-28402245

RESUMO

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 µg daily, or 25 µg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 µg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).


Assuntos
Hipotireoidismo/tratamento farmacológico , Tiroxina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Fadiga/etiologia , Feminino , Humanos , Hipotireoidismo/complicações , Análise de Intenção de Tratamento , Masculino , Qualidade de Vida , Tireotropina/sangue , Tiroxina/efeitos adversos , Tiroxina/sangue , Falha de Tratamento
19.
BMC Endocr Disord ; 17(1): 6, 2017 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-28158982

RESUMO

BACKGROUND: Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. METHODS: Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects <50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. DISCUSSION: This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. TRIAL REGISTRATION: Clinicaltrials.gov NCT01660126 ; registered 8th June 2012.


Assuntos
Terapia de Reposição Hormonal , Hipotireoidismo/tratamento farmacológico , Tiroxina/administração & dosagem , Idoso , Bancos de Sangue , Protocolos Clínicos , Método Duplo-Cego , Humanos , Segurança do Paciente
20.
Nature ; 542(7641): 295, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28202978
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA