Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 232
Filtrar
1.
Sci Rep ; 11(1): 2794, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531528

RESUMO

Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic associations of comorbid diseases within the framework of the Utrecht Cardiovascular Pharmacogenetic studies by turning information of > 25 years follow-up data of 1237 subjects whom were genotyped and included in the discovery study. We performed Cox proportional-hazards regression to examine associations between genetic variants and comorbid diseases including cardiovascular diseases (CVD), chronic eye disease, cancer, neurologic diseases and chronic kidney disease. Secondly, we replicated our findings in two independent cohorts consisting of 1041 subjects. Finally, we performed a meta-analysis by combining the discovery and two replication cohorts. We ascertained 390 (39.7%) incident cases of CVD, 182 (16.2%) of chronic eye disease, 155 (13.8%) of cancer, 31 (2.7%) of neurologic disease and 13 (1.1%) of chronic kidney disease during a median follow-up of 10.2 years. In the discovery study, we identified a total of 39 Single Nucleotide Polymorphisms (SNPs) associated with comorbid diseases. The replication study, confirmed that rs1870849 and rs8051326 may play a role in the incidence of chronic eye disease in T2D patients. Half of patients developed at least one comorbid disease, with CVD occurring most often and earliest followed by chronic eye disease. Further research is needed to confirm the associations of two associated SNPs with chronic eye disease in T2D.

3.
Cochrane Database Syst Rev ; 1: CD013496, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512717

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. Lifestyle changes are at the forefront of preventing the disease. This includes advice such as increasing physical activity and having a healthy balanced diet to reduce risk factors. Intermittent fasting (IF) is a popular dietary plan involving restricting caloric intake to certain days in the week such as alternate day fasting and periodic fasting, and restricting intake to a number of hours in a given day, otherwise known as time-restricted feeding. IF is being researched for its benefits and many randomised controlled trials have looked at its benefits in preventing CVD. OBJECTIVES: To determine the role of IF in preventing and reducing the risk of CVD in people with or without prior documented CVD. SEARCH METHODS: We conducted our search on 12 December 2019; we searched CENTRAL, MEDLINE and Embase. We also searched three trials registers and searched the reference lists of included papers. Systematic reviews were also viewed for additional studies. There was no language restriction applied. SELECTION CRITERIA: We included randomised controlled trials comparing IF to ad libitum feeding (eating at any time with no specific caloric restriction) or continuous energy restriction (CER). Participants had to be over the age of 18 and included those with and without cardiometabolic risk factors. Intermittent fasting was categorised into alternate-day fasting, modified alternate-day fasting, periodic fasting and time-restricted feeding. DATA COLLECTION AND ANALYSIS: Five review authors independently selected studies for inclusion and extraction. Primary outcomes included all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure. Secondary outcomes include the absolute change in body weight, and glucose. Furthermore, side effects such as headaches and changes to the quality of life were also noted. For continuous data, pooled mean differences (MD) (with 95% confidence intervals (CIs)) were calculated. We contacted trial authors to obtain missing data. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: Our search yielded 39,165 records after the removal of duplicates. From this, 26 studies met our criteria, and 18 were included in the pooled analysis. The 18 studies included 1125 participants and observed outcomes ranging from four weeks to six months. No studies included data on all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and heart failure at any point during follow-up. Of quantitatively analysed data, seven studies compared IF with ab libitum feeding, eight studies compared IF with CER, and three studies compared IF with both ad libitum feeding and CER. Outcomes were reported at short term (≤ 3 months) and medium term (> 3 months to 12 months) follow-up. Body weight was reduced with IF compared to ad libitum feeding in the short term (MD -2.88 kg, 95% CI -3.96 to -1.80; 224 participants; 7 studies; low-certainty evidence). We are uncertain of the effect of IF when compared to CER in the short term (MD -0.88 kg, 95% CI -1.76 to 0.00; 719 participants; 10 studies; very low-certainty evidence) and there may be no effect in the medium term (MD -0.56 kg, 95% CI -1.68 to 0.56; 279 participants; 4 studies; low-certainty evidence). We are uncertain about the effect of IF on glucose when compared to ad libitum feeding in the short term (MD -0.03 mmol/L, 95% CI -0.26 to 0.19; 95 participants; 3 studies; very-low-certainty of evidence) and when compared to CER  in the short term: MD -0.02 mmol/L, 95% CI -0.16 to 0.12; 582 participants; 9 studies; very low-certainty; medium term: MD 0.01, 95% CI -0.10 to 0.11; 279 participants; 4 studies; low-certainty evidence). The changes in body weight and glucose were not deemed to be clinically significant. Four studies reported data on side effects, with some participants complaining of mild headaches. One study reported on the quality of life using the RAND SF-36 score. There was a modest increase in the physical component summary score. AUTHORS' CONCLUSIONS: Intermittent fasting was seen to be superior to ad libitum feeding in reducing weight. However, this was not clinically significant. There was no significant clinical difference between IF and CER in improving cardiometabolic risk factors to reduce the risk of CVD. Further research is needed to understand the safety and risk-benefit analysis of IF in specific patient groups (e.g. patients with diabetes or eating disorders) as well as the effect on longer-term outcomes such as all-cause mortality and myocardial infarction.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Jejum , Adulto , Viés , Glicemia/metabolismo , Peso Corporal , Restrição Calórica/métodos , Jejum/efeitos adversos , Comportamento Alimentar , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Fatores de Tempo
4.
Hypertension ; 77(2): 383-392, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33356394

RESUMO

Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10-1.30]; P=4×10-5), peripheral artery disease (1.12 [95% CI, 1.03-1.21]; P=9×10-3), and stroke (1.11 [95% CI, 1.05-1.18]; P=2×10-4). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, -2.55 mm Hg [95% CI, -4.06 to -1.05]; P=1×10-3) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22-0.73]; P=3×10-3) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44-1.03]; P=0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.

5.
Blood ; 136(26): 3062-3069, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33367543

RESUMO

Fibrinogen is a key component of the coagulation cascade, and variation in its circulating levels may contribute to thrombotic diseases, such as venous thromboembolism (VTE) and ischemic stroke. Gamma prime (γ') fibrinogen is an isoform of fibrinogen that has anticoagulant properties. We applied 2-sample Mendelian randomization (MR) to estimate the causal effect of total circulating fibrinogen and its isoform, γ' fibrinogen, on risk of VTE and ischemic stroke subtypes using summary statistics from genome-wide association studies. Genetic instruments for γ' fibrinogen and total fibrinogen were selected, and the inverse-variance weighted MR approach was used to estimate causal effects in the main analysis, complemented by sensitivity analyses that are more robust to the inclusion of pleiotropic variants, including MR-Egger, weighted median MR, and weighted mode MR. The main inverse-variance weighted MR estimates based on a combination of 16 genetic instruments for γ' fibrinogen and 75 genetic instruments for total fibrinogen indicated a protective effect of higher γ' fibrinogen and higher total fibrinogen on VTE risk. There was also a protective effect of higher γ' fibrinogen levels on cardioembolic and large artery stroke risk. Effect estimates were consistent across sensitivity analyses. Our results provide evidence to support effects of genetically determined γ' fibrinogen on VTE and ischemic stroke risk. Further research is needed to explore mechanisms underlying these effects and their clinical applications.

6.
PLoS One ; 15(11): e0230035, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33186364

RESUMO

BACKGROUND: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome. METHODS AND RESULTS: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. For prevalent events, a total of 27,349 participants of European ancestry, including 1831 prevalent MI cases and 2518 prevalent CHD cases were used. For incident cases, a total of 55,736 participants of European ancestry were included (3,031 incident MI cases and 5,425 incident CHD cases). There were 1,860 all-cause deaths among the 3,751 MI and CHD cases from six cohorts that contributed to the analysis of all-cause mortality. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR = 1.80, 95% confidence interval: 1.43, 2.27; P = 7.12 × 10-7). We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) ≥ 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. CONCLUSION: This study identified one known locus (ANGPTL4) and four new loci (PLCL1, RC3H2, TMPRSS5, and LDLRAD1) associated with cardiovascular disease risk that warrant further investigation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33214188

RESUMO

INTRODUCTION: Pre-diabetes, a status conferring high risk of overt diabetes, is defined differently by the American Diabetes Association (ADA) and the WHO. We investigated the impact of applying definitions of pre-diabetes on lifetime risk of diabetes in women and men from the general population. RESEARCH DESIGN AND METHODS: We used data from 8844 women without diabetes and men aged ≥45 years from the prospective population-based Rotterdam Study in the Netherlands. In both gender groups, we calculated pre-diabetes prevalence according to ADA and WHO criteria and estimated the 10-year and lifetime risk to progress to overt diabetes with adjustment for competing risk of death. RESULTS: Out of 8844 individuals, pre-diabetes was identified in 3492 individuals (prevalence 40%, 95% CI 38% to 41%) according to ADA and 1382 individuals (prevalence 16%, 95% CI 15% to 16%) according to WHO criteria. In both women and men and each age category, ADA prevalence estimates doubled WHO-defined pre-diabetes. For women and men aged 45 years having ADA-defined pre-diabetes, the 10-year risk of diabetes was 14.2% (95% CI 6.0% to 22.5%) and 9.2% (95% CI 3.4% to 15.0%) compared with 23.2% (95% CI 6.8% to 39.6%) and 24.6% (95% CI 8.4% to 40.8%) in women and men with WHO-defined pre-diabetes. At age 45 years, the remaining lifetime risk to progress to overt diabetes was 57.5% (95% CI 51.8% to 63.2%) vs 80.2% (95% CI 74.1% to 86.3%) in women and 46.1% (95% CI 40.8% to 51.4%) vs 68.4% (95% CI 58.3% to 78.5%) in men with pre-diabetes according to ADA and WHO definitions, respectively. CONCLUSION: Prevalence of pre-diabetes differed considerably in both women and men when applying ADA and WHO pre-diabetes definitions. Women with pre-diabetes had higher lifetime risk to progress to diabetes. The lifetime risk of diabetes was lower in women and men with ADA-defined pre-diabetes as compared with WHO. Improvement of pre-diabetes definition considering appropriate sex-specific and age-specific glycemic thresholds may lead to better identification of individuals at high risk of diabetes.

8.
Sci Rep ; 10(1): 19940, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203906

RESUMO

Brain structure in later life reflects both influences of intrinsic aging and those of lifestyle, environment and disease. We developed a deep neural network model trained on brain MRI scans of healthy people to predict "healthy" brain age. Brain regions most informative for the prediction included the cerebellum, hippocampus, amygdala and insular cortex. We then applied this model to data from an independent group of people not stratified for health. A phenome-wide association analysis of over 1,410 traits in the UK Biobank with differences between the predicted and chronological ages for the second group identified significant associations with over 40 traits including diseases (e.g., type I and type II diabetes), disease risk factors (e.g., increased diastolic blood pressure and body mass index), and poorer cognitive function. These observations highlight relationships between brain and systemic health and have implications for understanding contributions of the latter to late life dementia risk.

9.
Nat Med ; 26(10): 1654-1662, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32839619

RESUMO

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart-brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.

10.
Neurology ; 95(14): e1963-e1970, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32817390

RESUMO

OBJECTIVE: To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD). METHODS: We conducted bidirectional 2-sample Mendelian randomization analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (n = 446,118), Psychiatric Genomics Consortium (n = 18,759), and International Genomics of Alzheimer's Project (n = 63,926). We used the inverse variance-weighted Mendelian randomization method to estimate causal effects and weighted median and Mendelian randomization-Egger for sensitivity analyses to test for pleiotropic effects. RESULTS: We found that higher risk of AD was significantly associated with being a "morning person" (odds ratio [OR] 1.01, p = 0.001), shorter sleep duration (self-reported: ß = -0.006, p = 1.9 × 10-4; accelerometer based: ß = -0.015, p = 6.9 × 10-5), less likely to report long sleep (ß = -0.003, p = 7.3 × 10-7), earlier timing of the least active 5 hours (ß = -0.024, p = 1.7 × 10-13), and a smaller number of sleep episodes (ß = -0.025, p = 5.7 × 10-14) after adjustment for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR 0.99, p = 7 × 10-13). However, we did not find evidence that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD. CONCLUSION: We found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.


Assuntos
Doença de Alzheimer/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Sono , Doença de Alzheimer/genética , Transtorno Depressivo Maior/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Fenótipo , Sono/genética
11.
Blood ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32722807

RESUMO

Fibrinogen is a key component of the coagulation cascade, and variation in its circulating levels may contribute to thrombotic diseases, such as venous thromboembolism (VTE) and ischemic stroke. Gamma prime (γ') fibrinogen is an isoform of fibrinogen that has anticoagulant properties. We applied two-sample Mendelian randomization (MR) to estimate the causal effect of total circulating fibrinogen and its isoform, γ' fibrinogen, on risk of VTE and ischemic stroke subtypes using summary statistics from genome-wide association studies. Genetic instruments for γ' fibrinogen and total fibrinogen were selected and the inverse-variance weighted MR approach was used to estimate causal effects in the main analysis, complemented by sensitivity analyses that are more robust to the inclusion of pleiotropic variants, including MR-Egger, weighted median MR, and weighted mode MR. The main inverse-variance weighted MR estimates based on a combination of 16 genetic instruments for γ' fibrinogen and 75 genetic instruments for total fibrinogen indicated a protective effect of higher γ' fibrinogen and higher total fibrinogen on VTE risk. There was also a protective effect of higher γ' fibrinogen levels on cardioembolic and large artery stroke risk. Effect estimates were consistent across sensitivity analyses. Our results provide evidence to support effects of genetically determined γ' fibrinogen on VTE and ischemic stroke risk. Further research is needed to explore mechanisms underlying these effects, and their clinical applications.

12.
Neurology ; 95(4): e353-e361, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32611631

RESUMO

OBJECTIVE: We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology. METHODS: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH). RESULTS: Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not ß-blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for calcium channel blockers showed particularly strong associations with small vessel stroke and the related radiologic phenotype of WMH. CONCLUSIONS: This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP-lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/complicações , Hipertensão/genética , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Pressão Sanguínea/genética , Doenças de Pequenos Vasos Cerebrais/etiologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana
13.
Environ Int ; 143: 105887, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32619912

RESUMO

The exposome concept refers to the totality of exposures from a variety of external and internal sources including chemical agents, biological agents, or radiation, from conception onward, over a complete lifetime. It encompasses also "psychosocial components" including the impact of social relations and socio-economic position on health. In this review we provide examples of recent contributions from exposome research, where we believe their application will be of the greatest value for moving forward. So far, environmental epidemiology has mainly focused on hard outcomes, such as mortality, disease exacerbation and hospitalizations. However, there are many subtle outcomes that can be related to environmental exposures, and investigations can be facilitated by an improved understanding of internal biomarkers of exposure and response, through the application of omic technologies. Second, though we have a wealth of studies on environmental pollutants, the assessment of causality is often difficult because of confounding, reverse causation and other uncertainties. Biomarkers and omic technologies may allow better causal attribution, for example using instrumental variables in triangulation, as we discuss here. Even more complex is the understanding of how social relationships (in particular socio-economic differences) influence health and imprint on the fundamental biology of the individual. The identification of molecular changes that are intermediate between social determinants and disease status is a way to fill the gap. Another field in which biomarkers and omics are relevant is the study of mixtures. Epidemiology often deals with complex mixtures (e.g. ambient air pollution, food, smoking) without fully disentangling the compositional complexity of the mixture, or with rudimentary approaches to reflect the overall effect of multiple exposures or components. From the point of view of disease mechanisms, most models hypothesize that several stages need to be transitioned through health to the induction of disease, but very little is known about the characteristics and temporal sequence of such stages. Exposome models reinforce the idea of a biography-to-biology transition, in that everyone's disease is the product of the individual history of exposures, superimposed on their underlying genetic susceptibilities. Finally, exposome research is facilitated by technological developments that complement traditional epidemiological study designs. We describe in depth one such new tools, adductomics. In general, the development of high-resolution and high-throughput technologies interrogating multiple -omics (such as epigenomics, transcriptomics, proteomics, adductomics and metabolomics) yields an unprecedented perspective into the impact of the environment in its widest sense on disease. The world of the exposome is rapidly evolving, though a huge gap still needs to be filled between the original expectations and the concrete achievements. Perhaps the most urgent need is for the establishment of a new generation of cohort studies with appropriately specified biosample collection, improved questionnaire data (including social variables), and the deployment of novel technologies that allow better characterization of individual environmental exposures, ranging from personal monitoring to satellite based observations.

14.
Hypertension ; 76(3): 683-691, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32623924

RESUMO

We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40-69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01-1.10) and 0.96 (0.92-1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings.

15.
BMC Public Health ; 20(1): 708, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32423423

RESUMO

BACKGROUND: The study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI. METHODS: We studied participants of Helsinki Birth Cohort Study born in 1934-1944 (HBCS1934-1944, n = 1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n = 5807, NFBC1986, n = 6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62 years in HBCS1934-1944, at 46 years in NFBC1966 and at 16 years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex. RESULTS: The association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (ß = 0.79, 95% CI, 0.33, 1.25, p < 0.001) in NFBC1966. In NFBC1986 this association was attenuated by PRS BMI (p = 0.181), and in HBCS1934-1944 there was no association between high early social disadvantage and increased later life BMI (ß 0.22, 95% CI -0.91,1.35, p = 0.700). In HBCS1934-1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (ß - 1.34, [- 2.37,-0.31], p = 0.011; ß - 0.46, [- 0.89,-0.03], p = 0.038, respectively). CONCLUSIONS: High social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.


Assuntos
Índice de Massa Corporal , Predisposição Genética para Doença/epidemiologia , Obesidade/epidemiologia , Classe Social , Idoso , Idoso de 80 Anos ou mais , Estatura , Estudos de Coortes , Feminino , Finlândia , Humanos , Modelos Lineares , Masculino , Fatores de Risco , Fatores Socioeconômicos
16.
Eur J Epidemiol ; 35(7): 699-707, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32440788

RESUMO

BACKGROUND: Live donor nephrectomy is a safe procedure. However, long-term donor prognosis is debated, necessitating high-quality studies. METHODS: A follow-up study of 761 living kidney donors was conducted, who visited the outpatient clinic and were propensity score matched and compared to 1522 non-donors from population-based cohort studies. Primary outcome was kidney function. Secondary outcomes were BMI (kg/m2), incidences of hypertension, diabetes, cardiovascular events, cardiovascular and overall mortality, and quality of life. RESULTS: Median follow-up after donation was 8.0 years. Donors had an increase in serum creatinine of 26 µmol/l (95% CI 24-28), a decrease in eGFR of 27 ml/min/1.73 m2 (95% CI - 29 to - 26), and an eGFR decline of 32% (95% CI 30-33) as compared to non-donors. There was no difference in outcomes between the groups for ESRD, microalbuminuria, BMI, incidence of diabetes or cardiovascular events, and mortality. A lower risk of new-onset hypertension (OR 0.45, 95% CI 0.33-0.62) was found among donors. The EQ-5D health-related scores were higher among donors, whereas the SF-12 physical and mental component scores were lower. CONCLUSION: Loss of kidney mass after live donation does not translate into negative long-term outcomes in terms of morbidity and mortality compared to non-donors. TRIAL REGISTRATION: Dutch Trial Register NTR3795.


Assuntos
Transplante de Rim/efeitos adversos , Rim/fisiologia , Doadores Vivos/psicologia , Nefrectomia/efeitos adversos , Qualidade de Vida/psicologia , Estudos de Casos e Controles , Creatinina/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Incidência , Testes de Função Renal , Doadores Vivos/estatística & dados numéricos , Masculino , Nefrectomia/psicologia , Vigilância da População , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Resultado do Tratamento
17.
Obesity (Silver Spring) ; 28(6): 1149-1156, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32379398

RESUMO

OBJECTIVE: People with diabetes show great variability in weight gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes were investigated. METHODS: A total of 6,223 participants from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class trajectories. RESULTS: During a mean follow-up of 13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMI were identified, including the "progressive overweight" group (n = 481, 85.1%), "progressive weight loss" group (n = 59, 10.4%), and "persistently high BMI" group (n = 25, 4.4%). The majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before diabetes diagnosis. The progressive weight loss group had fluctuations of glucose and marked beta cell function loss. The persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance accompanied by a rapid decrease of beta cell function. CONCLUSIONS: Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle-aged and elderly white population. Prevention strategies should be tailored rather than focusing only on high-risk individuals.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2/etiologia , Obesidade/classificação , Sobrepeso/classificação , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Fatores de Risco , Ganho de Peso , Perda de Peso
18.
Am J Clin Nutr ; 111(5): 1036-1047, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32232398

RESUMO

BACKGROUND: Obesity is associated with inflammation but the role of vitamin D in this process is not clear. OBJECTIVES: We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. METHODS: Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. RESULTS: In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. CONCLUSIONS: The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.


Assuntos
Obesidade/tratamento farmacológico , Vitamina D/análogos & derivados , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Análise da Randomização Mendeliana , Obesidade/epidemiologia , Obesidade/genética , Obesidade/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/administração & dosagem
19.
Eur Heart J ; 41(40): 3913-3920, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32076698

RESUMO

AIMS : Aortic valve stenosis is commonly considered a degenerative disorder with no recommended preventive intervention, with only valve replacement surgery or catheter intervention as treatment options. We sought to assess the causal association between exposure to lipid levels and risk of aortic stenosis. METHODS AND RESULTS : Causality of association was assessed using two-sample Mendelian randomization framework through different statistical methods. We retrieved summary estimations of 157 genetic variants that have been shown to be associated with plasma lipid levels in the Global Lipids Genetics Consortium that included 188 577 participants, mostly European ancestry, and genetic association with aortic stenosis as the main outcome from a total of 432 173 participants in the UK Biobank. Secondary negative control outcomes included aortic regurgitation and mitral regurgitation. The odds ratio for developing aortic stenosis per unit increase in lipid parameter was 1.52 [95% confidence interval (CI) 1.22-1.90; per 0.98 mmol/L] for low density lipoprotein (LDL)-cholesterol, 1.03 (95% CI 0.80-1.31; per 0.41 mmol/L) for high density lipoprotein (HDL)-cholesterol, and 1.38 (95% CI 0.92-2.07; per 1 mmol/L) for triglycerides. There was no evidence of a causal association between any of the lipid parameters and aortic or mitral regurgitation. CONCLUSION : Lifelong exposure to high LDL-cholesterol increases the risk of symptomatic aortic stenosis, suggesting that LDL-lowering treatment may be effective in its prevention.

20.
JAMA ; 323(7): 636-645, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068818

RESUMO

Importance: The incremental value of polygenic risk scores in addition to well-established risk prediction models for coronary artery disease (CAD) is uncertain. Objective: To examine whether a polygenic risk score for CAD improves risk prediction beyond pooled cohort equations. Design, Setting, and Participants: Observational study of UK Biobank participants enrolled from 2006 to 2010. A case-control sample of 15 947 prevalent CAD cases and equal number of age and sex frequency-matched controls was used to optimize the predictive performance of a polygenic risk score for CAD based on summary statistics from published genome-wide association studies. A separate cohort of 352 660 individuals (with follow-up to 2017) was used to evaluate the predictive accuracy of the polygenic risk score, pooled cohort equations, and both combined for incident CAD. Exposures: Polygenic risk score for CAD, pooled cohort equations, and both combined. Main Outcomes and Measures: CAD (myocardial infarction and its related sequelae). Discrimination, calibration, and reclassification using a risk threshold of 7.5% were assessed. Results: In the cohort of 352 660 participants (mean age, 55.9 years; 205 297 women [58.2%]) used to evaluate the predictive accuracy of the examined models, there were 6272 incident CAD events over a median of 8 years of follow-up. CAD discrimination for polygenic risk score, pooled cohort equations, and both combined resulted in C statistics of 0.61 (95% CI, 0.60 to 0.62), 0.76 (95% CI, 0.75 to 0.77), and 0.78 (95% CI, 0.77 to 0.79), respectively. The change in C statistic between the latter 2 models was 0.02 (95% CI, 0.01 to 0.03). Calibration of the models showed overestimation of risk by pooled cohort equations, which was corrected after recalibration. Using a risk threshold of 7.5%, addition of the polygenic risk score to pooled cohort equations resulted in a net reclassification improvement of 4.4% (95% CI, 3.5% to 5.3%) for cases and -0.4% (95% CI, -0.5% to -0.4%) for noncases (overall net reclassification improvement, 4.0% [95% CI, 3.1% to 4.9%]). Conclusions and Relevance: The addition of a polygenic risk score for CAD to pooled cohort equations was associated with a statistically significant, yet modest, improvement in the predictive accuracy for incident CAD and improved risk stratification for only a small proportion of individuals. The use of genetic information over the pooled cohort equations model warrants further investigation before clinical implementation.


Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Herança Multifatorial , Medição de Risco/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA