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1.
Diabetologia ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33650017

RESUMO

AIMS/HYPOTHESIS: Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, smaller bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to address these biases. Thus, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip. METHODS: We selected 35 SNPs strongly associated with fasting glucose (p < 5 × 10-8) in a non-diabetic European-descent population from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 133,010). MR was used to assess the associations of genetically predicted fasting glucose concentrations with total hip bone area and BMD in 4966 men and women without diabetes from the Swedish Mammography Cohort, Prospective Investigation of Vasculature in Uppsala Seniors and Uppsala Longitudinal Study of Adult Men. RESULTS: In a meta-analysis of the three cohorts, a genetically predicted 1 mmol/l increment of fasting glucose was associated with a 2% smaller total hip bone area (-0.67 cm2 [95% CI -1.30, -0.03; p = 0.039]), yet was also associated, albeit without reaching statistical significance, with a 4% higher total hip BMD (0.040 g/cm2 [95% CI -0.00, 0.07; p = 0.060]). CONCLUSIONS/INTERPRETATION: Fasting glucose may be a causal risk factor for smaller bone area at the hip, yet possibly for greater BMD. Further MR studies with larger sample sizes are required to corroborate these findings.

2.
Clin Nutr ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33610424

RESUMO

BACKGROUND AND AIMS: Each year, millions of people suffer from fragility fractures. Hip fractures are the most devastating type of such fractures. We aimed to investigate whether the association of dietary calcium intake with hip fracture risk can be modified by a healthy diet, herein defined as the modified Mediterranean diet score (mMED), in Swedish adults. METHODS: The study included 82,092 men and women at baseline. Diet and covariate data were collected twice, 12 years apart, using questionnaires. Information on incident hip fractures was collected from a national registry. Dietary calcium intake and mMED were each categorized into low, medium and high categories, and in nine combined strata of the two exposures. Multivariable adjusted hazard ratios (HR) of hip fracture with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression analysis, with time-updated information on exposures and covariates. Non-linear trends were assessed using restricted cubic splines. RESULTS: During 20 years of follow-up including 1,367,260 person-years at risk, 5938 individuals experienced a hip fracture. Dietary calcium intake and hip fracture were non-linearly associated, whereas adherence to mMED decreased hip fracture rates in a dose-response pattern. The lowest hip fracture rates were observed among women and men who reported a calcium intake of 800 mg or more, combined with a high adherence to mMED. In each stratum of calcium intake, the HRs of hip fracture were increasingly higher with lower adherence to mMED, compared with the reference level (high calcium and high mMED). Individuals with low calcium intake (<800 mg/day) or high calcium intake (>1200 mg/day) combined with low adherence to mMED had a HR of 1.54 (95% CI 1.28-1.85) and 1.50 (95% CI 1.26-1.77), respectively. No major differences in the hip fracture risk patterns were discerned between women and men. CONCLUSION: A moderate to high dietary calcium intake in the context of an overall healthy diet were associated with lower hip fracture rates.

3.
BMJ ; 371: m4337, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303475

RESUMO

OBJECTIVE: To investigate whether dog and cat owners and their pets share a risk of developing diabetes. DESIGN: Cohort study. SETTING: Register based longitudinal study, Sweden. PARTICIPANTS: 208 980 owner-dog pairs and 123 566 owner-cat pairs identified during a baseline assessment period (1 January 2004 to 31 December 2006). MAIN OUTCOME MEASURES: Type 2 diabetes events in dog and cat owners and diabetes events in their pets, including date of diagnosis during the follow-up period (1 January 2007 to 31 December 2012). Owners with type 2 diabetes were identified by combining information from the National Patient Register, the Cause of Death Register, and the Swedish Prescribed Drug Register. Information on diabetes in the pets was extracted from veterinary care insurance data. Multi-state models were used to assess the hazard ratios with 95% confidence intervals and to adjust for possible shared risk factors, including personal and socioeconomic circumstances. RESULTS: The incidence of type 2 diabetes during follow-up was 7.7 cases per 1000 person years at risk in dog owners and 7.9 cases per 1000 person years at risk in cat owners. The incidence of diabetes in the pets was 1.3 cases per 1000 dog years at risk and 2.2 cases per 1000 cat years at risk. The crude hazard ratio for type 2 diabetes in owners of a dog with diabetes compared with owners of a dog without diabetes was 1.38 (95% confidence interval 1.10 to 1.74), with a multivariable adjusted hazard ratio of 1.32 (1.04 to 1.68). Having an owner with type 2 diabetes was associated with an increased hazard of diabetes in the dog (crude hazard ratio 1.28, 1.01 to 1.63), which was attenuated after adjusting for owner's age, with the confidence interval crossing the null (1.11, 0.87 to 1.42). No association was found between type 2 diabetes in cat owners and diabetes in their cats (crude hazard ratio 0.99, 0.74 to 1.34, and 1.00, 0.78 to 1.28, respectively). CONCLUSIONS: Data indicated that owners of a dog with diabetes were more likely to develop type 2 diabetes during follow-up than owners of a dog without diabetes. It is possible that dogs with diabetes could serve as a sentinel for shared diabetogenic health behaviours and environmental exposures.

4.
Int J Epidemiol ; 2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33367703

RESUMO

BACKGROUND: We examined whether the inverse association between adherence to a Mediterranean diet and hip fracture risk is mediated by incident type 2 diabetes mellitus (T2DM) and body mass index (BMI). METHODS: We included 50 755 men and women from the Cohort of Swedish Men and the Swedish Mammography Cohort who answered lifestyle and medical questionnaires in 1997 and 2008 (used for calculation of the Mediterranean diet score 9mMED; low, medium, high) and BMI in 1997, and incident T2DM in 1997-2008). The cumulative incidence of hip fracture from the National Patient Register (2009-14) was considered as outcome. RESULTS: We present conditional odds ratios (OR) 9[95% confidence interval, CI) of hip fracture for medium and high adherence to mMED, compared with low adherence. The total effect ORs were 0.82 (0.71, 0.95) and 0.75 (0.62, 0.91), respectively. The controlled direct effect of mMED on hip fracture (not mediated by T2DM, considering BMI as an exposure-induced confounder), calculated using inverse probability weighting of marginal structural models, rendered ORs of 0.82 (0.72, 0.95) and 0.73 (0.60, 0.88), respectively. The natural direct effect ORs (not mediated by BMI or T2DM, calculated using flexible mediation analysis) were 0.82 (0.71, 0.95) and 0.74(0.61, 0.89), respectively. The path-specific indirect and partial indirect natural effects ORs (through BMI or T2DM) were close to 1. CONCLUSIONS: Mediterranean diet has a direct effect on hip fracture risk via pathways other than through T2DM and BMI. We cannot exclude mediating effects of T2DM or BMI, or that their effects cancel each other out.

5.
Nutrients ; 12(9)2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32872582

RESUMO

Osteoporosis and sarcopenia contribute to the risk of fracture in the population. These conditions share common features, and it is known that a healthy diet may have beneficial effects on both, theoretically resulting in fewer fractures. The present narrative review gives an overview of recent epidemiological research related to the association between healthy diets/dietary patterns, bone health and fragility fractures. The review also gives a brief overview on general dietary recommendations and advice as the cornerstone of public health nutrition. Although muscle health and sarcopenia contribute to the risk of fractures, these endpoints were not the focus of this review. Healthy diets are nutrient dense and contain bioactive components that are needed for the constant remodeling of the skeleton and to slow the rate of bone loss and muscle wasting, thus contributing to the prevention of fragility fractures. Compliance with healthy dietary patterns were predominantly found to be inversely associated with bone outcomes, although this was not entirely consistent across all studies. Different a priori diet scores, such as the Mediterranean diet score and the Dietary Inflammatory Index, as well as a posteriori data driven dietary patterns, such as the prudent or healthy dietary pattern, were inversely associated with fragility fractures in different populations. In conclusion, different healthy dietary patterns may contribute to bone health and less fractures. Following current dietary guidelines is thus advisable for the prevention of fragility fractures.

6.
Nutrients ; 12(9)2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32899514

RESUMO

Results indicating that a high milk intake is associated with both higher and lower risks of fragility fractures, or that indicate no association, can all be presented in the same meta-analysis, depending on how it is performed. In this narrative review, we discuss the available studies examining milk intake in relation to fragility fractures, highlight potential problems with meta-analyses of such studies, and discuss potential mechanisms and biases underlying the different results. We conclude that studies examining milk and dairy intakes in relation to fragility fracture risk need to study the different milk products separately. Meta-analyses should consider the doses in the individual studies. Additional studies in populations with a large range of intake of fermented milk are warranted.

7.
Nutrients ; 12(9)2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32927800

RESUMO

Milk and fermented milk consumption has been linked to health and mortality but the association with Parkinson's disease (PD) is uncertain. We conducted a study to investigate whether milk and fermented milk intakes are associated with incident PD. This cohort study included 81,915 Swedish adults (with a mean age of 62 years) who completed a questionnaire, including questions about milk and fermented milk (soured milk and yogurt) intake, in 1997. PD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers. Multivariable-adjusted hazard ratios were obtained from Cox proportional hazards regression models. During a mean follow-up of 14.9 years, 1251 PD cases were identified in the cohort. Compared with no or low milk consumption (<40 mL/day), the hazard ratios of PD across quintiles of milk intake were 1.29 (95% CI 1.07, 1.56) for 40-159 mL/day, 1.19 (95% CI 0.99, 1.42) for 160-200 mL/day, 1.29 (95% CI 1.08, 1.53) for 201-400 mL/day, and 1.14 (95% CI 0.93, 1.40) for >400 mL/day. Fermented milk intake was not associated with PD. We found a weak association between milk intake and increased risk of PD but no dose-response relationship. Fermented milk intake was not associated with increased risk of PD.

8.
PLoS Med ; 17(9): e1003331, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941436

RESUMO

BACKGROUND: It is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality. METHODS AND FINDINGS: Our longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997-2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20-24.9 kg/m2), overweight (25-29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6-8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson's weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96-1.11). In contrast, compared with those with normal weight and high mMED, individuals with a low mMED had a high mortality despite a normal BMI (HR 1.60; 95% CI 1.48-1.74). We found similar estimates among women and men. For CVD mortality (12,064 deaths) the findings were broadly similar, though obese individuals with high mMED retained a modestly increased risk of CVD death (HR 1.29; 95% CI 1.16-1.44) compared with those with normal weight and high mMED. A main limitation of the present study is the observational design with self-reported lifestyle information with risk of residual or unmeasured confounding (e.g., genetic liability), and no causal inferences can be made based on this study alone. CONCLUSIONS: These findings suggest that diet quality modifies the association between BMI and all-cause mortality in women and men. A healthy diet may, however, not completely counter higher CVD mortality related to obesity.


Assuntos
Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/mortalidade , Dieta Mediterrânea/psicologia , Idoso , Índice de Massa Corporal , Causas de Morte , Estudos de Coortes , Dieta Saudável , Feminino , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/dietoterapia , Sobrepeso , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar , Suécia
9.
Nutrients ; 12(5)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413977

RESUMO

Mortality in relation to type of milk intake is unclear. We present mortality rates by intake of non-fermented milk fat content type and examine the degree of bias when other fat content types of non-fermented milk are kept in the reference category. For this purpose, we used a longitudinal cohort consisting of 61,433 women who had been administered food frequency questionnaires in 1987-1990 and in 1997, and analyzed time to death. Non-fermented milk consumption was divided into low ≤0.5%, medium 1.5%, or high fat 3%. For each specific type of milk, the first analysis (A) is restricted to those who consumed less than one serving per day of the other milk subtypes. In the second analysis (B), everyone is retained, i.e., leading to a reference category "contaminated" with other milk consumers. During follow-up, 22,391 women died. Highest (≥3 glasses/day) vs. lowest consumption category of milk (<1 glass/day) with 0.5% fat content was associated with a multivariable hazard ratio (HR) of 1.71 (95%CI 1.57-1.86) in analysis A, whereas the same comparison with a "contaminated" reference category in analysis B provided a HR of 1.34 (95%CI 1.24-1.45), p-value for homogeneity <0.0001. The corresponding HRs for 1.5% fat milk were: 1.82 (95%CI 1.63-2.04) and 1.38 (95%CI 1.25-1.51), and for 3% fat milk 1.95 (95%CI 1.77-2.15) and 1.40 (95%CI 1.29-1.52). HR for ≥3 glasses/day of total milk was 1.95 (95%CI 1.84-2.06). We observe a higher mortality in women with high milk consumption, irrespective of milk fat content. A "contaminated" reference group substantially attenuates the actual estimates.

10.
Circ Cardiovasc Qual Outcomes ; 12(10): e005342, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31592725

RESUMO

BACKGROUND: Dog ownership is associated with increased physical activity levels and increased social support, both of which could improve the outcome after a major cardiovascular event. Dog ownership may be particularly important in single-occupancy households where ownership provides substitutive companionship and motivation for physical activity. METHODS AND RESULTS: We used the Swedish National Patient Register to identify all patients aged 40 to 85 presenting with an acute myocardial infarction (n=181 696; 5.7% dog ownership) or ischemic stroke (n=154 617; 4.8% dog ownership) between January 1, 2001 and December 31, 2012. Individual information was linked across registers for cause of death, sociodemographic, and dog ownership data. We evaluated all-cause mortality and risk of recurrent hospitalization for the same cause until December 31, 2012. Models were adjusted for socioeconomic, health, and demographic factors at study inclusion such as age, marital status, the presence of children in the home, area of residence, and income, as well as all registered comorbidities and hospitalization for cardiovascular disease in the past 5 years. Dog owners had a lower risk of death after hospitalization for acute myocardial infarction during the full follow-up period of 804 137 person-years, with an adjusted hazard ratio (HR) of 0.67 (95% CI, 0.61 to 0.75) for those who lived alone, and HR of 0.85 (95% CI, 0.80 to 0.90) for those living with a partner or a child. Similarly, after an ischemic stroke, dog owners were at lower risk of death during the full follow-up of 638 219 person-years adjusted HR of 0.73 (95% CI, 0.66 to 0.80) for those who lived alone and HR of 0.88 (95% CI, 0.83 to 0.93) for those living with a partner or a child. We further found an association of dog ownership with reduced risk of hospitalization for recurrent myocardial infarction (HR, 0.93; 95% CI, 0.87 to 0.99). CONCLUSIONS: We found evidence of an association of dog ownership with a better outcome after a major cardiovascular event. Although our models are adjusted for many potential confounders, there are also unmeasured confounders such as smoking that prevent us from drawing conclusions regarding a possible causal effect.


Assuntos
Isquemia Encefálica/mortalidade , Exercício Físico , Estilo de Vida Saudável , Infarto do Miocárdio/mortalidade , Animais de Estimação , Comportamento de Redução do Risco , Acidente Vascular Cerebral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/psicologia , Isquemia Encefálica/terapia , Causas de Morte , Cães , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/psicologia , Infarto do Miocárdio/terapia , Prognóstico , Estudos Prospectivos , Recidiva , Sistema de Registros , Fatores de Risco , Determinantes Sociais da Saúde , Apoio Social , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Suécia , Fatores de Tempo
11.
J Am Heart Assoc ; 8(11): e011860, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31433701

RESUMO

Background Mechanisms related to the influence of diet on the development of cardiovascular disease are not entirely understood, and protein biomarkers may help to understand these pathways. Studies of biomarkers identified with multiplex proteomic methods and dietary patterns are largely lacking. Methods and Results Dietary patterns were generated through principal component analysis in 2 population-based Swedish cohorts, the EpiHealth (EpiHealth study; n=20 817 men and women) and the SMCC (Swedish Mammography Cohort Clinical [n=4650 women]). A set of 184 protein cardiovascular disease biomarkers were measured with 2 high-throughput, multiplex immunoassays. Discovery and replication multivariable linear regression analyses were used to investigate the associations between the principal component analysis-generated dietary patterns and the cardiovascular disease-associated protein biomarkers, first in the EpiHealth (n=2240) and then in the Swedish Mammography Cohort Clinical. Four main dietary patterns were identified in the EpiHealth, and 3 patterns were identified in the Swedish Mammography Cohort Clinical. The healthy and the Western/traditional patterns were found in both cohorts. In the EpiHealth, 57 protein biomarkers were associated with 3 of the dietary patterns, and 41 of these associations were replicated in the Swedish Mammography Cohort Clinical, with effect estimates ranging from 0.057 to 0.083 (P-value range, 5.0×10-2-1.4×10-9) for each SD increase in the relative protein concentration. Independent associations were established between dietary patterns and the 21 protein biomarkers. Two proteins, myeloperoxidase and resistin, were associated with both the healthy and the light meal pattern but in opposite directions. Conclusions We have discovered and replicated independent associations between dietary patterns and 21 biomarkers linked to cardiovascular disease, which have a role in the pathways related to inflammation, endothelial and immune function, cell adhesion, and metabolism.


Assuntos
Proteínas Sanguíneas/análise , Doenças Cardiovasculares/sangue , Dieta , Comportamento Alimentar , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Dieta/efeitos adversos , Dieta Saudável , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Valor Nutritivo , Peroxidase/sangue , Proteômica , Resistina/sangue , Suécia/epidemiologia
12.
Eur J Prev Cardiol ; 26(17): 1865-1873, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31409108

RESUMO

AIMS: We aimed to discover and replicate associations between leisure-time physical activity and cardiovascular candidate plasma protein biomarkers and to examine whether the associations were independent of body fat. METHODS: We used cross-sectional data from two population-based cohorts, the EpiHealth (discovery cohort; n = 2239) and the Swedish Mammography Cohort - Clinical (SMCC; replication cohort; n = 4320). Physical activity during leisure time was assessed using questionnaires, and plasma concentrations of 184 proteins were assayed using the Olink Proseek Multiplex Cardiovascular 2 and 3 kits. We applied adjusted linear regression models using the False Discovery Rate to control for multiple testing in discovery. RESULTS: In EpiHealth, physical activity was associated with 75 cardiovascular plasma biomarkers, of which 28 associations were verified (replicated) in SMCC. Findings include seven novel associations in human: paraoxonase 3, cystatin B, cathepsin Z, alpha-L-iduronidase, prostasin, growth differentiation factor 2 and tumour necrosis factor alpha receptor superfamily member 11A. Estimates for associations were similar across tertiles of body fat and physical activity was associated with four biomarkers independent of body fat percentage: paraoxonase 3, cystatin B, fatty acid-binding protein 4 and interleukin-1 receptor antagonist. CONCLUSION: Leisure-time physical activity was associated with 28 cardiovascular-specific proteins; four associations were independent of body fat. Biomarkers in novel associations are involved in several atherosclerotic processes including regulation of low-density lipoprotein oxidation, protein degradation and immune cell adhesion and migration. Further research into these pathways may yield new insights into how physical activity affects cardiovascular health.


Assuntos
Proteínas Sanguíneas/metabolismo , Exercício Físico , Idoso , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Proteômica
13.
BMJ Open ; 9(3): e023447, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30850401

RESUMO

OBJECTIVE: To study the association between dog ownership and cardiovascular risk factors. DESIGN: A nationwide register-based cohort study and a cross-sectional study in a subset. SETTING: A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use. PARTICIPANTS: All Swedish residents aged 45-80 years on 1 October, 2006. MAIN OUTCOME MEASURES: Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus. RESULTS: After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45-60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status. CONCLUSIONS: In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Propriedade , Animais de Estimação , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Coortes , Intervalos de Confiança , Fatores de Confusão Epidemiológicos , Diabetes Mellitus/epidemiologia , Cães , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Estudos em Gêmeos como Assunto
14.
Am J Clin Nutr ; 109(2): 276-287, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30721968

RESUMO

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.


Assuntos
Tecido Adiposo/metabolismo , Composição Corporal/genética , Compartimentos de Líquidos Corporais/metabolismo , Músculo Esquelético/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Proteínas ADAMTS/genética , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Impedância Elétrica , Grupo com Ancestrais do Continente Europeu/genética , Proteínas da Matriz Extracelular/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/genética , Receptor Tipo 4 de Melanocortina/genética , Versicanas/genética , Adulto Jovem
15.
JBMR Plus ; 2(6): 367-374, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30460340

RESUMO

It is presently unclear whether free serum 25-hydroxyvitamin D (S-25(OH)D) better reflects bone health than total S-25(OH)D. We have previously shown that summer total S-25(OH)D values are more useful to predict bone mineral density (BMD) than winter values. Our objective was therefore to compare the relative importance of free and total S-25(OH)D for BMD by season. BMD was measured by dual-energy X-ray absorptiometry (DXA) in 5002 Swedish women (mean age 68 years) randomly selected from a large population-based longitudinal cohort study. Free S-25(OH)D was analyzed by a commercial ELISA and total S-25(OH)D by HPLC-tandem mass spectrometry (MS/MS). Free and total S-25(OH)D co-varied with season, with 26% and 29% higher values in August compared with those in January-March (nadir). There were no differences in mean BMD between categories of free or total S-25(OH)D in samples collected during winter. Women with higher total S-25(OH)D measured during summer had higher BMD at the total hip. Compared with women who had total S-25(OH)D values above 80 nmol/L during summer, adjusted BMD at the total hip was 6% (95% CI, 1% to 11%) lower for S-25(OH)D concentrations between 30 and 40 mmol/L, and 11% (95% CI, 3% to 19%) lower for those with total S-25(OH)D <30 nmol/L. In contrast, free S-25(OH)D measured during summer was not associated with BMD. Compared with women who had highest free S-25(OH)D measured during summer (>8.8 pmol/L), those with intermediate (2.4-3.5 pmol/L) and lowest (<2.4 pmol/L) free S-25(OH)D during summer did not have lower total hip BMD values (3% [95% CI, -2% to 7%] and -2% [95% CI, -8% to 4%]). In addition, we found no added value for the prediction of BMD with the combined measurement of total and free S-25(OH)D during summer or winter. We conclude that vitamin D status assessed by direct measurements of free S-25(OH)D does not reflect BMD better than total S-25(OH)D. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

16.
Calcif Tissue Int ; 103(5): 501-511, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29946974

RESUMO

Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip fracture, but the mechanisms are not fully understood. We aimed to investigate how T2DM, glucose, and insulin were associated with femoral bone mineral density (BMD), bone mineral area (BMA), and bone turnover markers. We used two cross-sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452, mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713, mean age 68 years). We identified men and women with normal fasting glucose (NFG), impaired fasting plasma glucose (IFG), and T2DM. BMD and BMA at the total hip and femoral shaft were measured using dual energy X-ray absorptiometry (DXA). Bone turnover markers; CrossLaps and osteocalcin were measured in women. Linear regression models were applied. Men and women showed a progressively higher BMD following the clinical cutoffs of fasting glucose from NFG to IFG to T2DM. In contrast, there was a progressively lower BMA. Men and women with T2DM, compared to those with NFG, had lower BMA at the total hip (- 1.7%; 95% CI - 3.2, - 0.2 and - 1.0%; 95% CI - 1.6, - 0.4) and the femoral shaft (- 2.0%; 95% CI - 3.5, - 0.4 and - 0.6%; 95% CI - 1.2, - 0.01), respectively. T2DM was associated with lower concentrations of CrossLaps (- 8.1%; 95% CI - 12.7, - 3.6) and osteocalcin (- 15.2%; 95% CI - 19.0, - 11.2). These cross-sectional results indicate that those with T2DM have smaller bone area and lower bone turnover, which could increase the risk of hip fracture.


Assuntos
Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Quadril , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Suécia
17.
J Bone Miner Res ; 33(10): 1842-1850, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29933501

RESUMO

It is not known how physical exercise affects the risk of different types of fractures, especially in highly active individuals. To investigate this association, we studied a cohort of 118,204 men and 71,757 women who from 1991 to 2009 participated in Vasaloppet, a long-distance cross-country skiing race in Sweden, and 505,194 nonparticipants frequency-matched on sex, age, and county of residence from the Swedish population. Participants ranged from recreational exercisers to world-class skiers. Race participation, distance of race run, number of races participated in, and finishing time were used as proxies for physical exercise. Incident fractures from 1991 to 2010 were obtained from national Swedish registers. Over a median follow-up of 8.9 years, 53,175 fractures of any type, 2929 hip, 3107 proximal humerus, 11,875 lower leg, 11,733 forearm, and 2391 vertebral fractures occurred. In a Cox proportional hazard regression analysis using time-updated exposure and covariate information, participation in the race was associated with an increased risk of any type of fracture (hazard ratio [HR], 1.02; 95% CI, 1.00 to 1.05); forearm fractures had an HR, 1.11 with a 95% CI, 1.06 to 1.15. There was a lower risk of hip (HR, 0.75; 95% CI, 0.67 to 0.83), proximal humerus (HR, 0.90; 95% CI, 0.82 to 0.98), and lower leg fractures (HR, 0.93; 95% CI, 0.89 to 0.97), whereas the HR of vertebral fracture was 0.97 with a 95% CI, 0.88 to 1.07. Among participants, the risk of fracture was similar irrespective of race distance and number of races run. Participants close to the median finishing time had a lower risk of fracture compared with faster and slower participants. In summary, high levels of physical exercise were associated with a slightly higher risk of fractures of any type, including forearm fractures, but a lower risk of hip, proximal humerus, and lower leg fractures. © 2018 American Society for Bone and Mineral Research.


Assuntos
Exercício Físico , Traumatismos do Antebraço/epidemiologia , Fraturas do Quadril/epidemiologia , Fraturas do Úmero/epidemiologia , Traumatismos da Perna/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia , Adulto Jovem
18.
Sci Rep ; 8(1): 7526, 2018 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-29760501

RESUMO

Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (ß = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; ß = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (Pheterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Cafeína/farmacologia , Cognição/efeitos dos fármacos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Memória/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/genética , Bancos de Espécimes Biológicos , Cafeína/farmacocinética , Café , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Variação Genética , Humanos , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Reino Unido
19.
Br J Nutr ; 119(7): 836-846, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29569544

RESUMO

High adherence to healthy diets has the potential to prevent disease and prolong life span, and healthy dietary pattern scores have each been associated with disease and mortality. We studied two commonly promoted healthy diet scores (modified Mediterranean diet score (mMED) and the Healthy Nordic Food Index (HNFI)) and the combined effect of the two scores in association with all-cause and cause-specific mortality (cancer, CVD and ischaemic heart disease). The study included 38 428 women (median age of 61 years) from the Swedish Mammography Cohort. Diet and covariate data were collected in a questionnaire. mMED and HNFI were generated and categorised into low-, medium- and high-adherence groups, and in nine combinations of these. Multivariable-adjusted hazard ratios (HR) of register-ascertained mortality and 95 % CI were calculated in Cox proportional hazards regression analysis. During follow-up (median: 17 years), 10 478 women died. In the high-adherence categories compared with low-adherence categories, the HR for all-cause mortality was 0·76 (95 % CI 0·70, 0·81) for mMED and 0·89 (95 % CI 0·83, 0·96) for HNFI. Higher adherence to mMED was associated with lower mortality in each stratum of HNFI in the combined analysis. In general, mMED, compared with HNFI, was more strongly associated with a lower cause-specific mortality. In Swedish women, both mMED and HNFI were inversely associated with all-cause and cardiovascular mortality. The combined analysis, however, indicated an advantage to be adherent to the mMED. The present version of HNFI did not associate with mortality independent of mMED score.


Assuntos
Dieta Saudável/normas , Dieta Mediterrânea , Mortalidade , Idoso , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Suécia
20.
Eur J Heart Fail ; 20(1): 55-62, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28967680

RESUMO

AIMS: To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology. METHODS AND RESULTS: Proteomic profiling (proximity extension assay) was performed in two community-based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0-70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9-78.1) years, 90 events]. Twenty-nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF-15), T-cell immunoglobulin and mucin domain 1 (TIM-1), tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), spondin-1 (SPON1), matrix metalloproteinase-12 (MMP-12), follistatin (FS), urokinase-type plasminogen activator surface receptor (U-PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF-15, U-PAR, MMP-12, TRAIL-R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM-1 was positively associated with worsened diastolic function (P < 0.02 for all). CONCLUSION: Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.


Assuntos
Proteínas Sanguíneas/metabolismo , Previsões , Insuficiência Cardíaca/sangue , Proteômica/métodos , Fatores Etários , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Suécia/epidemiologia
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