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1.
Int J Obes (Lond) ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945263

RESUMO

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35820201

RESUMO

BACKGROUND: The time during which there is an increased risk of death for cancer survivors was evaluated in a large twin study, which allows for matching on shared components such as age, genes, and socioeconomic factors in childhood. METHODS: By use of data from Danish registers, time to death from initial cancer was studied prospectively in twins in two different settings. The twins were diagnosed with at least one cancer in the period 1943-2011. Setting I included 5,680 same-sex twin pairs aged six and over, while Setting II included 3,218 twin individuals from age 70 and over. The study provides comparisons within twin pairs and across birth cohorts, age at diagnoses, and time at diagnosis. RESULTS: In 2001-2011, the five-year mortality risk for a twin surviving cancer after the age of 70 was twofold that of the co-twin, regardless of sex and zygosity, and it was 1.5-fold if the twin survived the initial nine months. After five to six years, the mortality risk corresponded to that of the co-twin. In previous decades, the excess hazard risk was considerably higher for both older and younger cohorts. There were no indications of change in relative survival across old birth cohorts. CONCLUSIONS: This large twin study suggested that for a cancer-treatment survivor diagnosed at age 70 or later, the additional mortality risk was largely absent five years later, by which time the survival relative to the co-twin was 60%. IMPACT: Elevated mortality risk after cancer is offset after five-six years.

4.
Sleep ; 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727734

RESUMO

While prior research has demonstrated a relationship between sleep and cognitive performance, how sleep relates to underlying genetic and environmental etiologies contributing to cognitive functioning, regardless of the level of cognitive function, is unclear. The present study assessed whether the importance of genetic and environmental contributions to cognition vary depending on an individual's aging-related sleep characteristics. The large sample consisted of twins from six studies within the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium spanning mid- to late-life (Average age (Mage)=57.6, range= 27 to 91 years, N=7052, Female=43.70%, 1525 complete monozygotic (MZ) pairs, 2001 complete dizygotic (DZ) pairs). Quantitative genetic twin models considered sleep duration as a primary moderator of genetic and environmental contributions to cognitive performance in four cognitive abilities (Semantic Fluency, Spatial-Visual Reasoning, Processing Speed, and Episodic Memory), while accounting for age moderation. Results suggested genetic and both shared and nonshared environmental contributions for Semantic Fluency and genetic and shared environmental contributions for Episodic Memory vary by sleep duration, while no significant moderation was observed for Spatial-Visual Reasoning or Processing Speed. Results for Semantic Fluency and Episodic Memory illustrated patterns of higher genetic influences on cognitive function at shorter sleep durations (i.e., 4 hours) and higher shared environmental contributions to cognitive function at longer sleep durations (i.e., 10 hours). Overall, these findings may align with associations of upregulation of neuroinflammatory processes and ineffective beta-amyloid clearance in short sleep contexts and common reporting of mental fatigue in long sleep contexts, both associated with poorer cognitive functioning.

5.
Arch Public Health ; 80(1): 161, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768834

RESUMO

BACKGROUND: Centenarians are used as a model of healthy ageing and longevity. Diet is a factor known to affect mortality in middle aged adults and elderly. However, it is unknown whether diet has an impact on survival to 100 + years. The aims of this systematic review were to summarize the evidence on (i) the association between dietary patterns in late adult life and survival to 100 + years and (ii) the common characteristics across dietary patterns that are shown to be positively associated with survival to 100 + years. METHODS: We performed a systematic literature search in MEDLINE and EMBASE, and a hand search at four longevity projects homepages up to 4 June 2021. We searched for cohort and case-control studies investigating the association between dietary patterns and all-cause mortality among individuals aged ≥ 65 years at enrolment regardless of their health status and residence. Studies were excluded if follow-up was performed too soon to allow the population or a subgroup of it to have become 100 + years of age. RESULTS: Of 3,685 identified records 108 reports were retrieved and full text screened. No studies met our inclusion criteria, thus the review process resulted in no eligible studies found. Hence, no risk of bias assessment and no synthesis of data was performed. CONCLUSIONS: No studies have investigated dietary patterns in late adult life in relation to survival to 100 + years of age. We have observed that as of June 2021 published cohort studies exist investigating all-cause mortality risk from different dietary patterns among the oldest old, but follow-up has been performed before the cohort could have reached 100 years of age. However, cohorts do exist where data on dietary habits in adult life has been collected decades ago and where follow-up in 2022 will allow the participants to have become 100 + years old. REGISTRATION: The review protocol is published at University of Southern Denmark's Research Portal (Poulsen et al. Dietary Patterns and Survival to 100 + Years: Protocol for a Systematic Review of cohort and case-control studies University of Southern Denmark's Research Portal: University of Southern Denmark, 2021) available at  https://portal.findresearcher.sdu.dk/en/publications/kostm%C3%B8nstre-og-overlevelse-til-100-%C3%A5r-protokol-for-en-systematisk . We have specified aim (i) of our research question in this report compared to the protocol, by adding "late" to "adult life".

6.
Neurosci Lett ; 784: 136737, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35709880

RESUMO

Extended maternal age has been suggested as marker of delayed age-associated disabilities. We use the Long Life Family Study (LLFS) offspring generation to investigate the association between extended maternal age at last childbirth and healthy-aging endophenotypes. We hypothesize that women with extended maternal age at last childbirth will exhibit healthier endophenotype profiles compared to younger mothers. The association between maternal age and age-related endophenotypes previously derived in LLFS was assessed using Generalized Estimating Equations to adjust for relatedness. The quartiles of the maternal age at last childbirth were modeled as the independent variables. Univariate analyses tested the association between maternal age at last childbirth and age at clinical assessment, education, field center, Apolipoprotein E (APOE) genotype, depression, stress, smoking and successful pregnancies. Only the variables significantly associated in the univariate analyses were considered in secondary multivariate analyses. Univariate analyses showed that compared to older mothers (age at last birth ≥35), mothers 30 years old or younger at last childbirth are less educated (12 ± 3 years versus 13 ± 3 years) and have a higher frequency of smoking (9% versus 3% for maternal age ≥35). Results showed that older mothers (age at last birth ≥31-34 or ≥ 35) demonstrated significantly better cognitive profiles (p = 0.017 and p = 0.021 respectively) compared with mothers with last childbirth age ≤30. Later maternal age among women from long-life families is associated with a better cognitive profile, supporting the hypothesis that later age at childbirth may be a marker for healthy aging.


Assuntos
Endofenótipos , Mães , Adulto , Escolaridade , Feminino , Humanos , Idade Materna , Gravidez , Fumar
7.
Am J Hum Genet ; 109(6): 1077-1091, 2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35580588

RESUMO

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.


Assuntos
Surdez , Perda Auditiva , Animais , Cóclea , Estudo de Associação Genômica Ampla , Perda Auditiva/genética , Humanos , Camundongos , Estria Vascular
8.
Aging Cell ; 21(6): e13608, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35546478

RESUMO

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10-7 , of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk after adjusting for clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed an improvement in prediction of cancer death with 5% increase in the C-index in a replication cohort, compared with the model including clinical risk factors alone. Mendelian randomization identified 15 putatively causal CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta = 1.2, PMR  = 4.1 × 10-4 ) and negatively associated with longevity (Beta = -1.9, PMR  = 0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune- and cancer-related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk.


Assuntos
Doenças Cardiovasculares , Neoplasias , Biomarcadores , Doenças Cardiovasculares/genética , Metilação de DNA/genética , Epigênese Genética , Epigenômica , Humanos , Masculino , Neoplasias/genética
9.
J Dev Orig Health Dis ; : 1-7, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35373734

RESUMO

The 'thrifty phenotype' hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.Anthropometric data were available on 7-34 year-old twins (n = 209, 97 males) and singletons (n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, -0.21, p = 0.055), weight (WAZ -0.73, p = 0.024) and BMI (BAZ -0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.

10.
Eur J Epidemiol ; 37(5): 495-502, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35394581

RESUMO

BACKGROUND: Living not just longer, but also cognitively healthier, and more independent lives is essential if European countries are to cope with the financial challenges that the shifting age composition of Europe's population presents. Here we investigate the change in life expectancy (LE) spent with good and poor cognitive function among older adults across Europe. METHODS: LE with good/poor cognitive function was estimated by the Sullivan Method. Cross-sectional data on cognitive functioning was obtained from 23,213 (wave 1, 2004-05) and 40,874 (wave 6, 2015) 50+-year-olds of the Survey of Health, Ageing and Retirement in Europe (SHARE). Information on mortality was obtained from the Eurostat Database. Results for 70+-year-olds were emphasized. RESULTS: LE with good cognitive function increased with 1.6 years from 10.7 years (95% CI: 10.6-10.9) in 2004-05 to 12.4 years (95% CI: 12.3-12.5) in 2015 for 70+-year-olds. Disparity was observed across sex and region. In 2004-05, a 70+-year-old woman could expect to spend 30.9% (95% CI: 29.4-32.4) of her remaining LE with poor cognitive function compared to 27.7% (95% CI: 26.0 -29.4) for men. In 2015, women (24.4% (95% CI: 23.4-25.3)) had considerably caught up with men (24.8% (95% CI:23.7.25.8)), shifting the pattern in favor of women. In 2004-05 and 2015, Northern Europeans had the lowest LE with poor cognitive function while Southern Europeans had the highest, but made the most improvement during the period. CONCLUSIONS: Overall we find that LE with poor cognitive function has been compressed in the European population of 70+-year-olds.


Assuntos
Envelhecimento , Expectativa de Vida , Idoso , Cognição , Estudos Transversais , Feminino , Humanos , Masculino , Aposentadoria
11.
Foot Ankle Surg ; 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35227591

RESUMO

BACKGROUND: It is unknown if genetics contribute to the etiology of acute Achilles tendon rupture (ATR). The aims of the present study were, 1) To calculate the concordance rate for monozygotic (MZ) twins and same-sex dizygotic (SSDZ) twins and 2) to estimate the heritability of ATR. METHODS: The study was performed as a registry study using the Danish Twin Registry and the Danish National Patient Registry. RESULTS: The study sample consisted of 85,534 twins born from 1895 to 1995. Of these, 572 (0.67%) were registered with ATR in the period from 1994 to 2014. The concordance rate was 8.1% (95% CI 1.4-14.7%) for MZ twins and 4.3% (95% CI 0.7-7.9%) for SSDZ twins. The heritability of ATR was 47% (95% CI 31-62%). CONCLUSION: This study found that genetics contribute substantially to the etiology of ATR with an estimated heritability of the liability to ATR of approximately 50%. The finding generates the hypothesis that genetics play a role in the pathological changes that occur in the Achilles tendon before a rupture. The risk of ATR for a twin within a 20 year period, if the co-twin has had an ATR, was 8% for MZ twins and 4% for SSDZ twins.

12.
Genet Epidemiol ; 46(3-4): 182-198, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35191549

RESUMO

Nonsyndromic orofacial clefts (OFCs) are among the most common craniofacial birth defects worldwide, and known to exhibit phenotypic and genetic heterogeneity. Cleft lip plus cleft palate (CLP) and cleft lip only (CL) are commonly combined together as one phenotype (CL/P), separately from cleft palate alone. In comparison, our study analyzes CL and CLP separately. A sample of 2218 CL and CLP cases, 4537 unaffected relatives of cases, and 2673 pure controls with no family history of OFC were selected from the Pittsburgh Orofacial Cleft (Pitt-OFC) multiethnic study.genome-wide association studies were run for seven specific phenotypes created based on the cleft type(s) observed within these families, as well as the combined CL/P phenotype. Five novel genome-wide significant associations, 3q29 (rs62284390), 5p13.2 (rs609659), 7q22.1 (rs6465810), 19p13.3 (rs628271), and 20q13.33 (rs2427238), and nine associations (p ≤ 1.0E-05) within previously confirmed OFC loci-PAX7, IRF6, FAM49A, DCAF4L2, 8q24.21, ARID3B, NTN1, TANC2 and the WNT9B:WNT3 gene cluster-were observed. We also found that single nucleotide polymorphisms within a subset of the associated loci, both previously known and novel, differ substantially in terms of their effects across cleft- or family-specific phenotypes, indicating not only etiologic differences between CL and CLP, but also genetic heterogeneity within each of the two OFC subtypes.


Assuntos
Fenda Labial , Fissura Palatina , Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Humanos , Fatores Reguladores de Interferon/genética , Fenótipo , Polimorfismo de Nucleotídeo Único
13.
Eur Geriatr Med ; 13(4): 977-986, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35218555

RESUMO

PURPOSE: Cardiovascular health among middle-aged and older people has improved in high-income countries. It is unknown whether this also applies for the oldest-old and if so, is it driven by better treatment or by a health improvement? Therefore, we compared two Danish centenarian birth cohorts born in 1895 and 1915, respectively, to investigate if the cardiovascular profile had improved in the most recent born cohort. METHODS: All individuals turning 100 years old in 1995 and 2015, respectively, were included with participation rates of 74% (n = 106) and 79% (n = 238), respectively. Data were collected through structured in-home interviews. Cardiovascular profile was obtained by measured blood pressure, electrocardiogram (ECG), and information on medication. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. RESULTS: Mean SBP and DBP were almost identical in the two cohorts. Yet, the prevalence of measured hypertension was non-significantly higher in the 1895 cohort [73%, 95% CI (61;82)] compared to the 1915 cohort [63%, 95% CI (55;70)]. The proportion receiving at least one type of cardiovascular drug was significantly higher in the 1915 cohort [80%, 95% CI (74;86)] compared to 1895 cohort [66%, 95% CI 55;76)]. ECG findings were similar in the two cohorts, e.g., atrial fibrillation was present in 17% of the 1895 cohort and 20% of the 1915 cohort. CONCLUSION: This comparison study found a non-significant improvement in measured hypertension irrespective of medical treatment in the recent born cohort. Also, the recent born cohort was treated more intensively with cardiovascular drugs than earlier. However, the prevalence of pathological ECG-findings was unchanged.

14.
Front Cell Dev Biol ; 10: 621261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223824

RESUMO

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect, affecting approximately 1 in 700 births. NSCL/P has complex etiology including several known genes and environmental factors; however, known genetic risk variants only account for a small fraction of the heritability of NSCL/P. It is commonly suggested that gene-by-environment (G×E) interactions may help explain some of the "missing" heritability of NSCL/P. We conducted a genome-wide G×E interaction study in cases and controls of European ancestry with three common maternal exposures during pregnancy: alcohol, smoking, and vitamin use using a two-stage design. After selecting 127 loci with suggestive 2df tests for gene and G x E effects, 40 loci showed significant G x E effects after correcting for multiple tests. Notable interactions included SNPs of 6q22 near VGLL2 with alcohol and 6p22.3 near PRL with smoking. These interactions could provide new insights into the etiology of CL/P and new opportunities to modify risk through behavioral changes.

16.
J Relig Health ; 61(2): 1621-1640, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32488829

RESUMO

Evidence of a possible association between religion and health in secular societies is sparse. We therefore conducted a nationwide study using data from 1596 Danes aged 50 + who participated in the Survey of Health, Ageing and Retirement in Europe (SHARE) wave 1 (2004-2005) and were followed up between 2006 and 2015, to investigate the association between religiousness and health including a lifestyle index. Results from the longitudinal models adjusted for age and gender showed that being religiously educated by parents, taking part in a religious organization, and praying were factors associated with fewer risk factors of unhealthy lifestyle. Furthermore, being religiously educated was associated with lower odds of self-rated poor health and depressive symptoms. Results were overall consistent across the cross-sectional and longitudinal models and persisted after further adjustment for education and marital status. These findings provide support for a positive relationship between religiousness and health among Danes, particularly for those being religiously educated by their parents.


Assuntos
Depressão , Aposentadoria , Envelhecimento , Estudos Transversais , Depressão/diagnóstico , Europa (Continente) , Humanos , Estilo de Vida , Estudos Longitudinais , Pessoa de Meia-Idade
17.
Aging Clin Exp Res ; 34(2): 367-374, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34196949

RESUMO

BACKGROUND: Fatigue, inflammation, and physical activity (PA) are all independently associated with gait speed, but their directionality is not fully elucidated. AIMS: Evaluate the bidirectional associations amongst fatigue, inflammation, and PA on gait speed. METHODS: This cross sectional study included probands (n = 1280, aged 49-105) and offspring (n = 2772, aged 24-88) in the Long Life Family Study. We assessed gait speed, fatigue with the question "I could not get going", inflammation using fasting interleukin-6 (IL-6) and high sensitivity C-reactive protein (CRP), and self-reported PA as walking frequency in the past two weeks. The two generations were examined separately using linear mixed modeling. RESULTS: Lower fatigue, lower IL-6, and greater PA were all associated with faster gait speed in both generations (all p < 0.05); lower CRP was only associated with faster gait speed in the offspring. PA explained the association of fatigue and gait speed via a 16.1% (95% CI 9.7%, 26.7%) attenuation of the direct associations for the probands and 9.9% (95% CI 6.3%, 18.8%) in the offspring. In addition, IL-6 explained more of the association of fatigue and gait speed than the association between PA and gait speed, via a 14.9% (95% CI 9.2%, 23.4%) attenuation of the direct association in the offspring only. DISCUSSION: Results revealed a potential directionality from fatigue to IL-6 to PA that may lead to faster gait speed. Future work should examine these relationships longitudinally to establish temporality and causality. CONCLUSIONS: Our findings support a signal that lowering fatigue and inflammation and increasing physical activity may delay functional decline.


Assuntos
Exercício Físico , Velocidade de Caminhada , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Fadiga , Marcha , Humanos , Inflamação
18.
J Am Med Dir Assoc ; 23(3): 507-513.e1, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34389336

RESUMO

OBJECTIVES: The aim was to examine the relationship between body mass index (BMI) and mortality in older hospitalized patients taking activities of daily living (ADLs) into account. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Nationwide population-based study of all patients aged ≥65 years admitted to Danish geriatric medical departments during 2005 to 2014 and included in the National Danish Geriatric Database. METHODS: Patients were followed until death, emigration, or study termination (December 31, 2015). Primary outcome was all-cause mortality. BMI and ADLs were routinely assessed on admission and linked at an individual level to the Danish national health registers. Kaplan-Meier analysis was used to estimate crude survival according to each BMI subcategory and Cox regression to examine the association with mortality adjusting for age, comorbidity, polypharmacy, ADLs, marital status, prior hospitalizations, and admission year. RESULTS: In total, 74,589 patients (63% women) were included aged [mean (SD)] 82.5 (7.5) years with BMI [mean (SD)] of 23.9 (5.1) kg/m2. During follow-up 51,188 died. Follow-up time was 191,972 person-years. Unadjusted and adjusted hazard ratio (HR) for overall, 30-day, and 1-year mortality decreased significantly with increasing BMI. In women, the highest adjusted HR (95% confidence interval) for overall mortality was seen for underweight patients (BMI <16) 1.83 (1.72-1.95) and the lowest for obesity grade II patients (BMI = 35.0-39.9) 0.66 (0.60-0.73) when using normal weight (BMI = 18.5-24.9) as reference. In men, the HR for BMI <16 and BMI = 35.0-39.9 were 1.98 (1.76-2.23) and 0.56 (0.49-0.65), respectively. CONCLUSIONS AND IMPLICATIONS: In hospitalized older patients, association between mortality and BMI did not show a U-shaped or J-shaped curve after adjustment of multiple confounders, including ADLs. Instead, mortality was highest in patients with low BMI and decreased with increasing BMI before leveling off in the obese range. Our study highlights the need for a debate and reassessment of what should be the ideal BMI in this vulnerable patient group.


Assuntos
Atividades Cotidianas , Obesidade , Idoso , Índice de Massa Corporal , Feminino , Hospitalização , Humanos , Masculino , Obesidade/complicações , Estudos Retrospectivos , Fatores de Risco
19.
J Gerontol A Biol Sci Med Sci ; 77(4): 717-727, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34739053

RESUMO

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006-2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M chip) followed by imputation was conducted. Visit 2 (2014-2017) repeated all Visit 1 protocols and added carotid ultrasonography of atherosclerotic plaque and wall thickness, additional cognitive testing, and perceived fatigability. On average, LLFS families show healthier aging profiles than reference populations, such as the Framingham Heart Study, at all age/sex groups, for many critical healthy aging phenotypes. However, participants are not uniformly protected. There is considerable heterogeneity among the pedigrees, with some showing exceptional cognition, others showing exceptional grip strength, others exceptional pulmonary function, etc. with little overlap in these families. There is strong heritability for key healthy aging phenotypes, both cross-sectionally and longitudinally, suggesting that at least some of this protection may be genetic. Little of the variance in these heritable phenotypes is explained by the common genome (GWAS + Imputation), which may indicate that rare protective variants for specific phenotypes may be running in selected families.


Assuntos
Atividades Cotidianas , Estudo de Associação Genômica Ampla , Estudos Transversais , Humanos , Longevidade/genética , Fenótipo
20.
Scand J Public Health ; 50(2): 199-204, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32880216

RESUMO

Aim: Our aim was to explore whether familial factors influence the risk of ischemic heart disease, stroke, and their co-occurrence. Methods: In total, 23,498 monozygotic and 39,540 same-sex dizygotic twins from the Danish Twin Registry were followed from 1977 to 2011 in the Danish National Patient Registry for ischemic heart disease and stroke. Time-to-event analyses accounting for censoring and competing risk of death were used to estimate familial risk (casewise concordance relative to the cumulative incidence) and heritability of ischemic heart disease, stroke, and the co-occurrence by age. Results: During follow-up, we observed 5561 and 4186 twin individuals with ischemic heart disease and stroke respectively, with 936 twin pairs concordant for ischemic heart disease and stroke. Familial risks were significant for both, with higher cumulative risks in monozygotic than in dizygotic twins. Estimates for heritability were significant for ischemic heart disease as well as for stroke diagnosed after the age of 80. The casewise concordance of ischemic heart disease in twins whose co-twin was diagnosed with stroke did not differ for monozygotic and dizygotic twins; however, from age 55 it was 10% higher than the cumulative risk in the overall twin cohort and was 25% higher at age 90. A similar pattern was seen for stroke following the co-twin's ischemic heart disease. Conclusions: As in previous studies, we found a higher heritability of ischemic heart disease than of stroke. There was a significant familial risk but no heritability for the co-occurrence of ischemic heart disease and stroke. The co-occurrence is therefore likely due to other shared familial than genetic factors, highlighting that preventive initiatives should target families rather than individuals.


Assuntos
Isquemia Miocárdica , Acidente Vascular Cerebral , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/genética , Sistema de Registros , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Gêmeos Monozigóticos/genética
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