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1.
PLoS One ; 14(10): e0224538, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31648270

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0194084.].

3.
Diabetologia ; 62(11): 1998-2006, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446444

RESUMO

AIMS/HYPOTHESIS: The pathogenesis of type 2 diabetes is not fully understood. We investigated whether circulating levels of preselected proteins were associated with the outcome 'diabetes' and whether these associations were causal. METHODS: In 2467 individuals of the population-based, cross-sectional EpiHealth study (45-75 years, 50% women), 249 plasma proteins were analysed by the proximity extension assay technique. DNA was genotyped using the Illumina HumanCoreExome-12 v1.0 BeadChip. Diabetes was defined as taking glucose-lowering treatment or having a fasting plasma glucose of ≥7.0 mmol/l. The associations between proteins and diabetes were assessed using logistic regression. To investigate causal relationships between proteins and diabetes, a bidirectional two-sample Mendelian randomisation was performed based on large, genome-wide association studies belonging to the DIAGRAM and MAGIC consortia, and a genome-wide association study in the EpiHealth study. RESULTS: Twenty-six proteins were positively associated with diabetes, including cathepsin D, retinal dehydrogenase 1, α-L-iduronidase, hydroxyacid oxidase 1 and galectin-4 (top five findings). Three proteins, lipoprotein lipase, IGF-binding protein 2 and paraoxonase 3 (PON-3), were inversely associated with diabetes. Fourteen of the proteins are novel discoveries. The Mendelian randomisation study did not disclose any significant causal effects between the proteins and diabetes in either direction that were consistent with the relationships found between the protein levels and diabetes. CONCLUSIONS/INTERPRETATION: The 29 proteins associated with diabetes are involved in several physiological pathways, but given the power of the study no causal link was identified for those proteins tested in Mendelian randomisation. Therefore, the identified proteins are likely to be biomarkers for type 2 diabetes, rather than representing causal pathways.

4.
Thorax ; 74(10): 958-964, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31434752

RESUMO

INTRODUCTION: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear. METHODS: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. RESULTS: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. CONCLUSION: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

5.
Int J Epidemiol ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363756

RESUMO

BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.

6.
Circulation ; 140(11): 910-920, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31446766

RESUMO

BACKGROUND: Studies have revealed a higher incidence of atrial fibrillation among well-trained athletes. We aim to investigate associations of endurance training with incidence of atrial fibrillation and stroke and to establish potential sex differences of such associations in a cohort of endurance trained athletes. METHODS: All Swedish skiers (208 654) completing 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989-2011) and a matched sample (n=527 448) of nonskiers were followed until first event of atrial fibrillation or stroke. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of atrial fibrillation and stroke. RESULTS: Female skiers in Vasaloppet had a lower incidence of atrial fibrillation than did female nonskiers (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), independent of finishing time and number of races. Male skiers had a similar incidence to that of nonskiers (HR, 0.98; 95% CI, 0.93-1.03). Skiers with the highest number of races or fastest finishing times had the highest incidence. Skiers of either sex had a lower incidence of stroke than did nonskiers (HR, 0.64; 95% CI, 0.60-0.67), independent of the number of races and finishing time. Skiers with atrial fibrillation had higher incidence of stroke than did skiers and nonskiers without atrial fibrillation (men: HR, 2.28; 95% CI, 1.93-2.70; women: HR, 3.51; 95% CI, 2.17-5.68; skiers with atrial fibrillation vs. skiers without atrial fibrillation). After diagnosis of atrial fibrillation, skiers with atrial fibrillation had a lower incidence of stroke (HR, 0.73; 95% CI, 0.50-0.91) and lower mortality compared with nonskiers with atrial fibrillation (HR, 0.57; 95% CI, 0.49-0.65). CONCLUSIONS: Female skiers in Vasaloppet had lower incidence of atrial fibrillation and stroke. Male skiers had similar incidence of atrial fibrillation and lower risk of stroke. Men with higher number of races and faster finishing times had the highest incidence of atrial fibrillation. After diagnosis of atrial fibrillation, skiers had lower incidence of stroke and death than did nonskiers with atrial fibrillation. This indicates that although on an individual level atrial fibrillation in well-trained individuals is associated with higher incidence of stroke, on population level, risk of stroke is low and that exercise should not be avoided.

7.
Int J Cardiol ; 296: 1-7, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31303394

RESUMO

BACKGROUND: Low density lipoprotein cholesterol (LDL-C) goals post-myocardial infarction (MI) are debated, and the significance of achieved blood lipid levels for predicting a first recurrent atherosclerotic cardiovascular disease (rASCVD) event post-MI is unclear. METHODS: This was a cohort study on first-ever MI survivors aged ≤76 years attending 4-14 week revisits throughout Sweden 2005-2013. Personal-level data was collected from SWEDEHEART and linked national registries. Exposures were quintiles of LDL-C, high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs) at the revisit. Group level associations with rASCVD (nonfatal MI or coronary heart disease death or fatal or nonfatal ischemic stroke) were estimated in Cox regression models. Predictive capacity was estimated by differences in C-statistic, integrated discriminatory improvement, and net reclassification improvement when adding each blood lipid to a validated risk prediction model. RESULTS: 25,643 patients, 96.9% on statin therapy, were followed during a mean of 4.1 years. rASCVD occurred in 2173 patients (8.5%). For LDL-C and TC, moderate associations with rASCVD were observed only in the 5th vs. the lowest (referent) quintiles. For TGs and HDL-C increased risks were observed in quintiles 3-5 vs. the lowest. Minor predictive improvements were observed when lipid fractions were added to the risk model but the discrimination overall was poor (C-statistics <0.6). CONCLUSIONS: Our data question the importance of LDL-C levels achieved at first revisit post-MI for decisions on continued treatment intensity considering the weak association with rASCVD observed in this post-MI cohort.

8.
J Cardiovasc Pharmacol ; 73(6): 352-358, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31162243

RESUMO

Antihypertensive drugs (AHTDs) and statins are frequently administered together, but there is uncertainty on whether the presence of one affects the main effects of the other. This systematic review and meta-analysis assessed the effects of co-administered AHTDs and statins on blood pressure (BP) and cholesterol. MEDLINE, Cochrane Central Register of Controlled Trials and drug regulatory agency websites were searched, until January 2018. Twelve double-blind randomized controlled trials that allocated adults with or without hypertension and/or hyperlipidemia (n = 4434) to fixed doses of AHTD alone, statin alone and both drugs together, for ≥4 weeks, were included. BP lowering was similar with AHTD + statin compared with AHTD alone [systolic BP -0.1 mm Hg, 95% confidence interval (CI), -1.0 to 0.8, and diastolic BP -1.0 mm Hg, 95% CI, -2.3 to -0.2]. AHTD + statin compared with statin alone resulted in small reduction in low-density lipoprotein cholesterol (-3.9 mg/dL, 95% CI, -6.1 to -1.7), and this effect was largely associated with co-administration of amlodipine and atorvastatin or rosuvastatin. There was no difference in safety outcomes. Overall, it can be concluded that there is no clinically important difference in the effects of AHTDs and statins whether used separately or together for reduction in BP and low-density lipoprotein cholesterol.

9.
ESC Heart Fail ; 6(4): 764-773, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148414

RESUMO

AIMS: We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction. METHODS AND RESULTS: Mass spectrometry-based metabolomic profiling was performed in plasma or serum samples from three community-based cohorts without heart failure at baseline (total n = 3924; 341 incident heart failure events; median follow-up ranging from 4.6 to 13.9 years). Cox proportional hazard models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) (n = 920) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n = 1121). Replication was undertaken in the independent cohort TwinGene (n = 1797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low-density and high-density lipoprotein cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow-up). Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age-adjusted and sex-adjusted models in the discovery and replication sample. The hazard ratio for urobilin in the replication cohort was estimated to 1.29 per standard deviation unit, 95% confidence interval (CI 1.03-1.63), and for sphingomyelin (30:1) to 0.72 (95% CI 0.58-0.89). Results remained similar after further adjustment for established heart failure risk factors in meta-analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (ß = -0.70, 95% CI -1.03 to -0.38). No major improvement in risk prediction was observed when adding the top 2 metabolites (C-index 0.787, 95% CI 0.752-0.823) or nine Lasso-selected metabolites (0.790, 95% CI 0.754-0.826) to a modified Atherosclerosis Risk in Communities heart failure risk score model (0.780, 95% CI 0.745-0.816). CONCLUSIONS: Our metabolomic profiling of three community-based cohorts study identified associations of circulating levels of the haem breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

10.
J Hypertens ; 37(8): 1699-1704, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31058795

RESUMO

OBJECTIVES: As intervention studies have shown a reduction in body weight to be paralleled with a reduction in left ventricular mass (LVM), we quantified a hypothesized causal relationship between fat mass and LVM, and how much of these effects that was mediated by blood pressure (BP), diabetes and adipokines. Also visceral and subcutaneous adipose tissue (VAT and SAT) were explored in the same fashion. METHODS: In the Prospective Study of the Vasculature in Uppsala Seniors study (n = 1016, 50% women, all aged 70 years), LVM was measured by echocardiography (indexed for lean mass, LVMI), fat and lean mass by dual-energy X-ray. VAT and SAT were measured by abdominal MRI (in n = 275). RESULTS: In a structural equation model adjusting for sex, the total effect of fat mass on LVMI was large (standardized coefficient 0.280, P = 3.2 × 10, 95% confidence interval 0.210-0.349). Out of the total effect of fat mass on LVMI, 29.0% was mediated by BP and glucose (P = 2.4 × 10). The BP pathway was most important, mediating 24.4% of the total effect of fat mass on LVMI (P = 4.6 × 10), while the glucose pathway accounted for 4.6% (P = 0.033). The association of VAT with LVMI (0.202, P = 2.4 × 10) was slightly weaker than that of SAT with LVMI (0.283, P = 1.0 × 10). Of several measured adipokines, leptin was a significant mediator of the effect of fat mass on LVMI (P = 3.0 × 10). CONCLUSION: One-third of the hypothesized association between body fat and LVMI was mediated by BP and glucose in this population-based cohort. Leptin was also an important mediator. Visceral adipose tissue was not more closely related to LVMI than subcutaneous abdominal fat.

11.
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.

12.
PLoS One ; 14(2): e0212060, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30802263

RESUMO

BACKGROUND: A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels. MATERIAL AND METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured. RESULTS: Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships. CONCLUSION: The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.

13.
Nat Commun ; 10(1): 29, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30604766

RESUMO

Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.


Assuntos
Taxa de Filtração Glomerular/genética , Hipertensão/genética , Cálculos Renais/genética , Rim/fisiopatologia , Insuficiência Renal Crônica/genética , Adulto , Idoso , Pressão Sanguínea/genética , Grupos Étnicos/genética , Feminino , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Código das Histonas/genética , Histonas/metabolismo , Humanos , Hipertensão/etnologia , Hipertensão/fisiopatologia , Cálculos Renais/etnologia , Cálculos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/etnologia , Insuficiência Renal Crônica/fisiopatologia
14.
JAMA Cardiol ; 4(2): 163-173, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649175

RESUMO

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

15.
Ups J Med Sci ; 124(1): 46-50, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30689485

RESUMO

In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.


Assuntos
Pesquisa Comparativa da Efetividade/métodos , Controle de Medicamentos e Entorpecentes , Projetos de Pesquisa , Ensaios Clínicos como Assunto , Pesquisa Comparativa da Efetividade/economia , Análise Custo-Benefício , Coleta de Dados , Aprovação de Drogas , Indústria Farmacêutica , Humanos , Estudos Observacionais como Assunto , Farmacoepidemiologia , Pontuação de Propensão , Estudos Prospectivos , Saúde Pública , Suécia/epidemiologia
16.
Ups J Med Sci ; 124(1): 21-28, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30618330

RESUMO

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.


Assuntos
Sistema de Registros , Pesquisa Biomédica/métodos , Estudos de Coortes , Ética Médica , Estudos de Associação Genética , Humanos , Cooperação Internacional , Avaliação de Resultados (Cuidados de Saúde) , Projetos Piloto , Modelos de Riscos Proporcionais , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/epidemiologia , Suécia/epidemiologia
17.
J Hypertens ; 37(1): 216-222, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30339551

RESUMO

OBJECTIVE: As endothelial dysfunction is an early event in atherosclerosis formation, we investigated if proteins previously related to cardiovascular disease also were related to endothelial function using a novel targeted proteomics approach. METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 850-970, all aged 70 years), endothelium-dependent vasodilation (EDV) in the forearm was assessed by intra-arterial infusion of acetylcholine. Flow-mediated vasodilation (FMD) was investigated in the brachial artery by ultrasound. The same investigations were carried out in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 375-461, all aged 50 years). After strict quality control, 84 cardiovascular-related proteins measured by the proximity extension assay were studied in relation to EDV and FMD in PIVUS (discovery sample) and POEM (validation sample). RESULTS: Of the 15 proteins being significantly related to EDV in PIVUS (false discovery rate <0.025), seven could be replicated in POEM at nominal significance and same effect direction when adjusted for sex and storage time. Of those, only cathepsin D remained significant following further adjustment for traditional cardiovascular risk factors (beta, -0.08; 95% confidence interval, -0.16, -0.01; P = 0.033; change in ln-transformed EDV per 1-SD increase in protein level). No protein was significantly related to FMD. CONCLUSION: Using a discovery/validation approach in two samples, our results indicate an inverse association between plasma cathepsin D levels and endothelial-dependent vasodilation.

18.
J Hypertens ; 37(1): 16-23, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30499920

RESUMO

OBJECTIVE: To assess the clinical relevance of regression to the mean for clinical trials and clinical practice. METHODS: MEDLINE was searched until February 2018 for randomized trials of BP lowering with over 1000 patient-years follow-up per group. We estimated baseline mean BP, follow-up mean (usual) BP amongst patients grouped by 10 mmHg strata of baseline BP, and assessed effects of BP lowering on coronary heart disease (CHD) and stroke according to these BP levels. RESULTS: Eighty-six trials (349 488 participants), with mean follow-up of 3.7 years, were included. Most mean BP change was because of regression to the mean rather than treatment. At high baseline BP levels, even after rigorous hypertension diagnosis, downwards regression to the mean caused much of the fall in BP. At low baseline BP levels, upwards regression to the mean increased BP levels, even in treatment groups. Overall, a BP reduction of 6/3 mmHg lowered CHD by 14% (95% CI 11-17%) and stroke by 18% (15-22%), and these treatment effects occurred at follow-up BP levels much closer to the mean than baseline BP levels. In particular, more evidence was available in the SBP 130-139 mmHg range than any other range. Benefits were apparent in numerous high-risk patient groups with baseline mean SBP less than 140 mmHg. CONCLUSION: Clinical practice should focus less on pretreatment BP levels, which rarely predict future untreated BP levels or rule out capacity to benefit from BP lowering in high cardiovascular risk patients. Instead, focus should be on prompt, empirical treatment to maintain lower BP for those with high BP and/or high risk.

19.
Ups J Med Sci ; : 1-8, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30468101

RESUMO

BACKGROUND: Regular exercise reduces pulse rate, but it is less clear how prolonged sitting time affects pulse rate. Our hypothesis was that high physical activity could compensate for prolonged sitting time regarding the pulse rate. METHODS: Regression analysis was performed on cross-sectional data including 47,457 men and women based on two Swedish cohort studies, EpiHealth (18-45 years) and LifeGene (45-75 years). Self-reported leisure time physical activity was given in five levels, from low (level 1) to vigorous (level 5), and television time was used as a proxy of sitting time. RESULTS: A higher physical activity (level 4 compared to level 1) was associated with a lower pulse rate in middle-aged females (-2.7 beats per minute [bpm]; 95% CI -3.3 to -2.2) and males (-4.0 bpm; 95% CI -4.7 to -3.4). The relationship between physical activity and pulse rate was strongest in the young. A prolonged television time (3 h compared to 1 h per day) was associated with a slightly higher pulse rate in middle-aged females (+0.6 bpm; 95% CI +0.3 to +0.8) and males (+0.9 bpm; 95% CI +0.7 to +1.2). Among participants with a prolonged television time (3 h), those with a high physical activity (level 4) had a lower pulse rate compared to those with a low physical activity (level 1). CONCLUSIONS: A prolonged television time was associated with a high pulse rate, while high physical activity was associated with a low pulse rate. The results suggest that a high physical activity could compensate for a prolonged television time regarding pulse rate.

20.
BMC Med Inform Decis Mak ; 18(1): 106, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458757

RESUMO

BACKGROUND: Common measures used to describe preventive treatment effects today are proportional, i.e. they compare the proportions of events in relative or absolute terms, however they are not easily interpreted from the patient's perspective and different magnitudes do not seem to clearly discriminate between levels of effect presented to people. METHODS: In this randomised cross-sectional survey experiment, performed in a Swedish population-based sample (n = 1041, response rate 58.6%), the respondents, aged between 40 and 75 years were given information on a hypothetical preventive cardiovascular treatment. Respondents were randomised into groups in which the treatment was described as having the effect of delaying a heart attack for different periods of time (Delay of Event, DoE): 1 month, 6 months or 18 months. Respondents were thereafter asked about their willingness to initiate such therapy, as well as questions about how they valued the proposed therapy. RESULTS: Longer DoE:s were associated with comparatively greater willingness to initiate treatment. The proportions accepting treatment were 81, 71 and 46% when postponement was 18 months, 6 months and 1 month respectively. In adjusted binary logistic regression models the odds ratio for being willing to take therapy was 4.45 (95% CI 2.72-7.30) for a DoE of 6 months, and 6.08 (95% CI 3.61-10.23) for a DoE of 18 months compared with a DoE of 1 month. Greater belief in the necessity of medical treatment increased the odds of being willing to initiate therapy. CONCLUSIONS: Lay people's willingness to initiate preventive therapy was sensitive to the magnitude of the effect presented as DoE. The results indicate that DoE is a comprehensible effect measure, of potential value in shared clinical decision-making.

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