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2.
J Am Med Dir Assoc ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31409558

RESUMO

OBJECTIVES: Studies examining the associations between oral health and disability have limited oral health measures. We investigated the association of a range of objectively and subjectively assessed oral health markers with disability and physical function in older age. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses were based on the British Regional Heart Study (BRHS) comprising men aged 71 to 92 years (n = 2147) from 24 British towns, and the Health, Aging, and Body Composition (HABC) Study comprising men and women aged 71 to 80 years (n = 3075) from the United States. Assessments included oral health (periodontal disease, tooth count, dry mouth, and self-rated oral health), disability, and physical function (grip strength, gait speed, and chair stand test). RESULTS: In the BRHS, dry mouth, tooth loss, and cumulative oral health problems (≥3 problems) were associated with mobility limitations and problems with activities of daily living and instrumental activities of daily living; these remained significant after adjustment for confounding variables (for ≥3 dry mouth symptoms, odds ratio (OR) 2.68, 95% confidence interval (CI) 1.94-3.69; OR 1.76, 95% CI 1.15-2.69; OR 2.90, 95% CI 2.01, 4.18, respectively). Similar results were observed in the HABC Study. Dry mouth was associated with the slowest gait speed in the BRHS, and the weakest grip strength in the HABC Study (OR 1.75, 95% CI 1.22, 2.50; OR 2.43, 95% CI 1.47-4.01, respectively). CONCLUSIONS AND IMPLICATIONS: Markers of poor oral health, particularly dry mouth, poor self-rated oral health, and the presence of more than 1 oral health problem, were associated with disability and poor physical function in older populations. Prospective investigations of these associations and underlying pathways are needed.

3.
Nat Commun ; 10(1): 3669, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413261

RESUMO

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

4.
Cancer Causes Control ; 30(10): 1057-1065, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401707

RESUMO

PURPOSE: As obesity and type 2 diabetes (T2D) have been increasing worldwide, we investigated their association with breast cancer incidence in the Reykjavik Study. METHODS: During 1968-1996, approximately 10,000 women (mean age = 53 ± 9 years) completed questionnaires and donated blood samples. T2D status was classified according to self-report (n = 140) and glucose levels (n = 154) at cohort entry. A linkage with the Icelandic Cancer Registry provided breast cancer incidence through 2015. Cox regression with age as time metric and adjusted for known confounders was applied to obtain hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Of 9,606 participants, 294 (3.1%) were classified as T2D cases at cohort entry while 728 (7.8%) women were diagnosed with breast cancer during 28.4 ± 11.6 years of follow-up. No significant association of T2D (HR 0.95; 95% CI 0.56-1.53) with breast cancer incidence was detected except among the small number of women with advanced breast cancer (HR 3.30; 95% CI 1.13-9.62). Breast cancer incidence was elevated among overweight/obese women without (HR 1.18; 95% CI 1.01-1.37) and with T2D (HR 1.35; 95% CI 0.79-2.31). Height also predicted higher breast cancer incidence (HR 1.03; 95% CI 1.02-1.05). All findings were confirmed in women of the AGES-Reykjavik sub-cohort (n = 3,103) who returned for an exam during 2002-2006. With a 10% T2D prevalence and 93 incident breast cancer cases, the HR for T2D was 1.18 (95% CI 0.62-2.27). CONCLUSIONS: These findings in a population with low T2D incidence suggest that the presence of T2D does not confer additional breast cancer risk and confirm the importance of height and excess body weight as breast cancer risk factors.

5.
PLoS One ; 14(8): e0221474, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31442261

RESUMO

BACKGROUND: The debate whether "asymptomatic hyperuricemia" should be treated is still ongoing. The objective of this cross-sectional study was to analyze whether hyperuricema in the elderly is associated with joint pain. METHODS AND FINDINGS: Participants in the population-based AGES-Reykjavik Study (males 2195, females 2975, mean age 76(6)) answered standardized questions about joint pain. In addition they recorded intermittent hand joint pain by marking a diagram of the hand. In males, no association was found between hyperuricemia and pain. Females however, showed a positive association between hyperuricemia and joint pain at many sites. After adjustment for age, BMI and hand osteoarthritis however, only intermittent hand joint pain (OR 1.30(1.07-1.58), p = 0.008) and intermittent pain in ≥10 hand joints (OR 1.75(1.32-2.31), p<0.001) remained significant. The best model for describing the relationship between serum uric acid levels (SUA) and intermittent hand joint pain in ≥10 joints was non-linear with a cut-off at 372 µmol/L. The attributable surplus number of symptomatic females with SUA ≥372 µmol/L was approximately 2.0% of the study population for those reporting pain in ≥10 hand joints. Next after having severe hand osteoarthritis, SUA ≥372 was an independent predictive factor of intermittent pain in ≥10 hand joints. Intermittent hand joint pain was also an independent risk factor for worse general health description. CONCLUSION: Results from this population based study indicate that hyperuricemia in elderly females may be a rather frequent cause of intermittent hand joint pain, often in many joints. The most likely explanation relates to low-grade urate crystal induced inflammation. Our data do not allow for assessment of the severity of symptoms or whether they merit specific treatment, but intermittent hand joint pain was an independent predictor of worse general health. These findings may be an important contribution to the debate on whether hyperuricemia should be treated.

6.
PLoS One ; 14(7): e0219668, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31356640

RESUMO

BACKGROUND: Apolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-ε2 allele on diseases in the elderly and survival remains elusive. METHODS: We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-ε2, with survival in the population. RESULTS: During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1*10-2), whereas APOE-ε4 carriers were at increased risk of death (HR 1.17,1.12-1.21; P = 2.8*10-16). APOE was associated with mortality risk in a dose-dependent manner, with risk estimates lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). After censoring for dementia, effect estimates remained similar for APOE-ε2 (HR 0.95,0.90-1.01), but attenuated for APOE-ε4 (HR 1.07,1.01-1.12). Results were broadly similar across cohorts, and did not differ by age or sex. APOE genotype was associated with baseline lipid fractions (e.g. mean difference(95%CI) in LDL(mg/dL) for ε2 versus ε33: -17.1(-18.1-16.0), and ε4 versus ε33: +5.7(4.8;6.5)), but the association between APOE and mortality was unaltered after adjustment for baseline LDL or cardiovascular disease. Given the European ancestry of the study population, results may not apply to other ethnicities. CONCLUSION: Compared with APOE-ε3, APOE-ε2 is associated with prolonged survival, whereas mortality risk is increased for APOE-ε4 carriers. Further collaborative efforts are needed to unravel the role of APOE and in particular APOE-ε2 in health and disease.

7.
Cancer ; 125(16): 2877-2885, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31179538

RESUMO

BACKGROUND: The World Cancer Research Fund classifies as "strong evidence" the link between obesity and the risk of advanced prostate cancer. In light of the different hormonal profiles associated with where adipose is stored, this study investigated the role of objectively measured body fat distribution and the risk of clinically relevant prostate cancer. METHODS: This was a prospective study of 1832 men in the Age, Gene/Environment Susceptibility-Reykjavik study. From 2002 to 2006, participants underwent baseline computed tomography imaging of fat deposition, bioelectric impedance analysis, and measurement of body mass index (BMI) and waist circumference. Men were followed through linkage with nationwide cancer registries for the incidence of total (n = 172), high-grade (Gleason grade ≥8; n = 43), advanced (≥cT3b/N1/M1 at diagnosis or fatal prostate cancer over follow-up; n = 41), and fatal prostate cancer (n = 31) through 2015. Cox regression was used to evaluate the association between adiposity measures and prostate cancer outcomes. RESULTS: Among all men, visceral fat (hazard ratio [HR], 1.31 per 1-standard deviation [SD] increase; 95% confidence interval [CI], 1.00-1.72) and thigh subcutaneous fat (HR, 1.37 per 1-SD increase; 95% CI, 1.00-1.88) were associated with risk of advanced and fatal disease, respectively. Among men who were leaner based on BMI, visceral fat was associated with both advanced and fatal disease. BMI and waist circumference were associated with a higher risk of advanced and fatal disease. No adiposity measures were associated with total or high-grade disease. CONCLUSIONS: Specific fat depots as well as BMI and waist circumference were associated with the risk of aggressive prostate cancer, which may help to elucidate underlying mechanisms and target intervention strategies.

9.
Am J Hum Genet ; 105(1): 15-28, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31178129

RESUMO

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

10.
Nutrients ; 11(5)2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058834

RESUMO

One-third of cancers can be prevented through healthy lifestyles. This study investigates the prevalence of and factors associated with engagement in cancer prevention guidelines in a population-based cohort of 2124 older white and black men and women. We used Health ABC data to construct a score from 0 (lowest adherence) to 7 (greatest adherence) based on the sum of seven recommendations for cancer prevention from the World Cancer Research Fund/American Institute for Cancer Research; body fatness (maintenance of healthy body weight), physical activity (at least moderately physically active), diet (fruit, vegetables, fiber, and red and processed meat), and alcohol. Mean (SD) scores in men and women were 3.24 (1.09) and 3.17 (1.10). Lower scores were associated with younger age (women only), black race, current smoking, and prevalent cardiovascular disease. Less than 1% of men and women adhered to all recommendations. Of the individual guidelines, adherence was lowest for fiber (9% of men; 6% of women) followed by physical activity (26% of men; 18% of women), and body weight (21% of men; 26% of women). These results suggest a critical public health need, especially given the growing older population. Black older adults, smokers, and those with prevalent disease may be at higher risk and thus warrant additional focus.

11.
Nicotine Tob Res ; 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31091312

RESUMO

INTRODUCTION: In addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development (RTD) - a measure of muscle power in older adults. METHODS: Data from 4469 older adults, aged 66-95 years at baseline in the Age, Gene/Environment Susceptibility - Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history and potential covariates were analyzed. RESULTS: Sex-differences were observed in these data, therefore our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with = -0.10, 95% CI -0.17, -0.03 and = -0.19, 95% CI -0.33, -0.05, respectively) and lower muscle attenuation (i.e., higher fat infiltration, = -0.08, 95% CI -0.16, -0.01 and = -0.17, 95% CI -0.34, -0.01, respectively) when compared to never-smokers. Smoking status was not associated with male peak torque or RTD. In women, current smoking was associated with lower muscle attenuation (= -0.24, 95% CI -0.34, -0.13) compared to never-smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years. CONCLUSIONS: Results suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women. IMPLICATIONS: This manuscript presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation.This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, due to its known association with poor physical function, falls, and hip fractures.

12.
Am J Clin Nutr ; 109(4): 1216-1223, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982858

RESUMO

BACKGROUND: Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed. OBJECTIVE: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies. METHODS: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants. RESULTS: There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides. CONCLUSIONS: Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.

13.
Ann Intern Med ; 170(10): 673-681, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31035288

RESUMO

Background: Poor olfaction is common among older adults and has been linked to higher mortality. However, most studies have had a relatively short follow-up and have not explored potential explanations. Objective: To assess poor olfaction in relation to mortality in older adults and to investigate potential explanations. Design: Community-based prospective cohort study. Setting: 2 U.S. communities. Participants: 2289 adults aged 71 to 82 years at baseline (37.7% black persons and 51.9% women). Measurements: Brief Smell Identification Test in 1999 or 2000 (baseline) and all-cause and cause-specific mortality at 3, 5, 10, and 13 years after baseline. Results: During follow-up, 1211 participants died by year 13. Compared with participants with good olfaction, those with poor olfaction had a 46% higher cumulative risk for death at year 10 (risk ratio, 1.46 [95% CI, 1.27 to 1.67]) and a 30% higher risk at year 13 (risk ratio, 1.30 [CI, 1.18 to 1.42]). Similar associations were found in men and women and in white and black persons. However, the association was evident among participants who reported excellent to good health at baseline (for example, 10-year mortality risk ratio, 1.62 [CI, 1.37 to 1.90]) but not among those who reported fair to poor health (10-year mortality risk ratio, 1.06 [CI, 0.82 to 1.37]). In analyses of cause-specific mortality, poor olfaction was associated with higher mortality from neurodegenerative and cardiovascular diseases. Mediation analyses showed that neurodegenerative diseases explained 22% and weight loss explained 6% of the higher 10-year mortality among participants with poor olfaction. Limitation: No data were collected on change in olfaction and its relationship to mortality. Conclusion: Poor olfaction is associated with higher long-term mortality among older adults, particularly those with excellent to good health at baseline. Neurodegenerative diseases and weight loss explain only part of the increased mortality. Primary Funding Source: National Institutes of Health and Michigan State University.

14.
J Sports Sci ; 37(15): 1746-1754, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30929574

RESUMO

Dynamic sitting, such as fidgeting and desk work, might be associated with health, but remains difficult to identify out of accelerometry data. We examined, in a laboratory study, whether dynamic sitting can be identified out of triaxial activity counts. Among 18 participants (56% men, 27.3 ± 6.5 years), up to 236 counts per minute were recorded in the anteroposterior and mediolateral axes during dynamic sitting using a hip-worn accelerometer. Subsequently, we examined in 621 participants (38% men, 80.0 ± 4.7 years) from the AGES-Reykjavik Study whether dynamic sitting was associated with cardio-metabolic health. Compared to participants who recorded the fewest dynamic sitting minutes (Q1), those with more dynamic sitting minutes had a lower BMI (Q2 = -1.39 (95%CI = -2.33;-0.46); Q3 = -1.87 (-2.82;-0.92); Q4 = -3.38 (-4.32;-2.45)), a smaller waist circumference (Q2 = -2.95 (-5.44;-0.46); Q3 = -3.47 (-6.01;-0.93); Q4 = -8.21 (-10.72;-5.71)), and a lower odds for the metabolic syndrome (Q2 = 0.74 [0.45;1.20] Q3 = 0.58 [0.36;0.95]; Q4 = 0.36 [0.22;0.59]). Our findings suggest that dynamic sitting might be identified using accelerometry and that this behaviour was associated with health. This might be important given the large amounts of time people spend sitting. Future studies with a focus on validation, causation and physiological pathways are needed to further examine the possible relevance of dynamic sitting.


Assuntos
Acelerometria/instrumentação , Metabolismo Energético , Exercício/fisiologia , Comportamento Sedentário , Postura Sentada , Adolescente , Adulto , Índice de Massa Corporal , Feminino , Monitores de Aptidão Física , Humanos , Masculino , Síndrome Metabólica , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura , Adulto Jovem
15.
Am J Clin Nutr ; 109(3): 535-543, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30850837

RESUMO

BACKGROUND: A higher protein intake is suggested to preserve muscle mass during aging and may therefore reduce the risk of sarcopenia. OBJECTIVES: We explored whether the amount and type (animal or vegetable) of protein intake were associated with 5-y change in mid-thigh muscle cross-sectional area (CSA) in older adults (n = 1561). METHODS: Protein intake was assessed at year 2 by a Block food-frequency questionnaire in participants (aged 70-79 y) of the Health, Aging, and Body Composition (Health ABC) Study, a prospective cohort study. At year 1 and year 6 mid-thigh muscle CSA in square centimeters was measured by computed tomography. Multiple linear regression analysis was used to examine the association between energy-adjusted protein residuals in grams per day (total, animal, and vegetable protein) and muscle CSA at year 6, adjusted for muscle CSA at year 1 and potential confounders including prevalent health conditions, physical activity, and 5-y change in fat mass. RESULTS: Mean (95% CI) protein intake was 0.90 (0.88, 0.92) g · kg-1 · d-1 and mean (95% CI) 5-y change in muscle CSA was -9.8 (-10.6, -8.9) cm2. No association was observed between energy-adjusted total (ß = -0.00; 95% CI: -0.06, 0.06 cm2; P = 0.982), animal (ß = -0.00; 95% CI: -0.06, 0.05 cm2; P = 0.923), or plant (ß = +0.07; 95% CI: -0.06, 0.21 cm2; P = 0.276) protein intake and muscle CSA at year 6, adjusted for baseline mid-thigh muscle CSA and potential confounders. CONCLUSIONS: This study suggests that a higher total, animal, or vegetable protein intake is not associated with 5-y change in mid-thigh muscle CSA in older adults. This conclusion contradicts some, but not all, previous research. This trial was registered at www.trialregister.nl as NTR6930.

16.
Disabil Health J ; 12(3): 495-502, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30871954

RESUMO

BACKGROUND: Physical function and physical activity decrease with age, but differences in physical activity patterns within different physical functioning groups are unknown. OBJECTIVES: To describe physical activity patterns and multimorbidity burden by physical function group and age. METHODS: Actigraph accelerometer-derived physical activity patterns were compared by physical function (high functioning, activity limitations, activity of daily living disabled) determined by questionnaire and age among 2174 older adults (mean age = 70.9, sd = 0.2 years) from the cross-sectional 2003-2006 National Health and Nutrition Examination Survey. Associations between physical function, physical activity, and multimorbidity were examined. RESULTS: Reduced physical function and increased age were associated with lower physical activity, increased sedentary time and a compressed activity profile. During the most active hour of the day (11:00 a.m.), the oldest, lowest physical functioning group was 82% less active than the youngest, highest physical functioning group. High functioning had over 30% more total activity counts, over 56% more time in moderate-to-vigorous activity, about 8% less time sedentary and took approximately one more sedentary break/hour than lower physical functioning groups. Gender differences in physical activity variables were prevalent for high functioning, but limited within reduced physical functioning groups. Physical function, age, total activity counts/day, and breaks in sedentary time/day were independently associated with multimorbidity (p < 0.005). CONCLUSIONS: Reduced physical function and increased age are associated with physical activity levels, and all three are associated with multimorbidity. Understanding physical activity differences by physical function is important for designing interventions for older individuals at increased risk for mobility disability.

17.
Cancer Causes Control ; 30(4): 333-342, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30805814

RESUMO

PURPOSE: Our main aim was to explore whether pre-diagnostic circulating levels of 25-hydroxyvitamin D (25(OH)D) among older individuals with cancer were associated with overall and cancer-specific survival after diagnosis. DESIGN: We used data from the Reykjavik-AGES Study on participants (n = 4,619) without cancer at entry, when blood samples were taken for 25(OH)D standardized measurements. The association with cancer risk, all-cause- and cancer-specific mortality was assessed among those later diagnosed with cancer, comparing four 25(OH)D categories, using 50-69.9 nmol/L as the reference category. RESULTS: Cancer was diagnosed in 919 participants on average 8.3 years after blood draw. No association was observed between the reference group and other 25(OH)D groups and total cancer incidence. Mean age at diagnosis was 80.9 (± 5.7) years. Of those diagnosed, 552 died during follow-up, 67% from cancer. Low pre-diagnostic levels of 25(OH)D < 30 nmol/L were significantly associated with increased total mortality (HR: 1.39, 95% CI 1.03, 1.88) and non-significantly with cancer-specific mortality (HR: 1.33, 95% CI 0.93, 1.90). Among patients surviving more than 2 years after diagnosis, higher pre-diagnostic 25(OH)D levels (≥ 70 nmol/L) were associated with lower risk of overall (HR: 0.68, 95% CI 0.46, 0.99) and cancer-specific mortality (HR: 0.47, 95% CI 0.26, 0.99). CONCLUSIONS: Among elderly cancer patients, low pre-diagnostic serum 25(OH)D levels (< 30 nmol/L) were associated with increased overall mortality.


Assuntos
Neoplasias/patologia , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Neoplasias/sangue , Risco , Sobrevida , Vitamina D/sangue , Deficiência de Vitamina D/sangue
18.
Eur J Hum Genet ; 27(6): 952-962, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30679814

RESUMO

Genome-wide association studies (GWAS) of quantitative electrocardiographic (ECG) traits in large consortia have identified more than 130 loci associated with QT interval, QRS duration, PR interval, and heart rate (RR interval). In the current study, we meta-analyzed genome-wide association results from 30,000 mostly Dutch samples on four ECG traits: PR interval, QRS duration, QT interval, and RR interval. SNP genotype data was imputed using the Genome of the Netherlands reference panel encompassing 19 million SNPs, including millions of rare SNPs (minor allele frequency < 5%). In addition to many known loci, we identified seven novel locus-trait associations: KCND3, NR3C1, and PLN for PR interval, KCNE1, SGIP1, and NFKB1 for QT interval, and ATP2A2 for QRS duration, of which six were successfully replicated. At these seven loci, we performed conditional analyses and annotated significant SNPs (in exons and regulatory regions), demonstrating involvement of cardiac-related pathways and regulation of nearby genes.

19.
Nutrients ; 11(1)2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30609725

RESUMO

The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15⁻1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80⁻2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision.


Assuntos
Predisposição Genética para Doença , Análise da Randomização Mendeliana , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida/genética , Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-Amida/metabolismo , Colestanotriol 26-Mono-Oxigenase/genética , Colestanotriol 26-Mono-Oxigenase/metabolismo , Estudos de Coortes , Família 2 do Citocromo P450/genética , Família 2 do Citocromo P450/metabolismo , Europa (Continente) , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Polimorfismo de Nucleotídeo Único , Vitamina D/sangue
20.
Lipids Health Dis ; 18(1): 7, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621701

RESUMO

BACKGROUND: Lipids are implicated in the pathogenesis of age-related macular degeneration (AMD). The relationship between systemic lipids and AMD has not been well characterized. The objective was to investigate the relationship between serum lipids and AMD in older adults using a lipidomic approach. METHODS: In a case-control study, 240 adults, aged ≥66 years, a third each having geographic atrophy, neovascular AMD, or no signs of AMD, were selected from a population-based sample of participants in the Age Gene/Environment Susceptibility-Reykjavik Study. The exposure was serum lipids and risk factors for AMD. The outcome was late AMD, assessed through fundus images taken through dilated pupils using a 45-degree digital camera and grading for neovascular AMD and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. RESULTS: Of 177 serum lipid species measured, there were no significant differences in serum lipids between controls and those with geographic atrophy or neovascular AMD, respectively. Adults with neovascular AMD had higher total serum lysophosphatidylcholine (LPC) (P = 0.004) and serum LPC 18:0 (P = 0.0002) compared to those with geographic atrophy. CONCLUSION: Late AMD was not characterized by alterations in systemic lipids compared with normal controls. These findings suggest that there may be differences in the LPC pathway between adults with neovascular AMD and geographic atrophy.


Assuntos
Atrofia Geográfica/sangue , Degeneração Macular/sangue , Neovascularização Retiniana/sangue , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Atrofia Geográfica/diagnóstico , Atrofia Geográfica/patologia , Humanos , Lisofosfatidilcolinas/sangue , Degeneração Macular/diagnóstico , Degeneração Macular/patologia , Masculino , Neovascularização Retiniana/diagnóstico , Neovascularização Retiniana/patologia , Fatores de Risco , Índice de Gravidade de Doença
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