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1.
Nutrients ; 12(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066363

RESUMO

It has been suggested that high intake of added sugar and sugar-sweetened beverages (SSBs) increase the level of circulating inflammatory proteins and that chronic inflammation plays a role in type 2 diabetes (T2D) development. We aim to examine how added sugar and SSB intake associate with 136 measured plasma proteins and C-reactive protein (CRP) in the Malmö Diet and Cancer-Cardiovascular Cohort (n = 4382), and examine if the identified added sugar- and SSB-associated proteins associate with T2D incidence. A two-step iterative resampling approach was used to internally replicate proteins that associated with added sugar and SSB intake. Nine proteins were identified to associate with added sugar intake, of which only two associated with T2D incidence (p < 0.00045). Seven proteins were identified to associate with SSB intake, of which six associated strongly with T2D incidence (p < 6.9 × 10-8). No significant associations were observed between added sugar and SSB intake and CRP concentrations. In summary, our elucidation of the relationship between plasma proteome and added sugar and SSB intake, in relation to future T2D risk, demonstrated that SSB intake, rather than the total intake of added sugar, was related to a T2D-pathological proteomic signature. However, external replication is needed to verify the findings.

2.
Nat Metab ; 2(10): 1135-1148, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33067605

RESUMO

Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.

3.
Atherosclerosis ; 313: 70-75, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33032235

RESUMO

BACKGROUND AND AIMS: The aim of the study was to determine potential associations between endothelial dysfunction and arterial stiffness, measured by peripheral arterial tonometry, and coronary artery calcium score (CACS) assessed by computed tomography (CT). METHODS AND RESULTS: The BIG3 study is a prospective longitudinal, non-interventional, pulmonary-cardiovascular cohort study exploring the three major smoking-induced diseases: cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, in a 45-75 aged cohort (mean 62 years), enriched in smokers. Computed tomography of the chest with assessment of CACS was performed in a selected subset of the participants (n = 2080). Peripheral arterial tonometry (EndoPAT) was used to assess endothelial function and arterial stiffness measured as reactive hyperaemia index (RHI) and augmentation index (AI), respectively. We observed significant associations of CACS, endothelial dysfunction, and arterial stiffness with several risk factors for coronary heart disease including age, sex, BMI, diabetes mellitus, and blood pressure. There was significant association of CACS, classified into three levels of severity, with RHI and AI (p = 0.0005 and p = 0.0009, respectively). For groups of increasing CACS (0, 1-400 and > 400 Agatston score), RHI decreased from median 1.89 (1.58-2.39), and 1.93 (1.62-2.41) to 1.77 (1.51-2.10). AI increased from median 14.3 (5.7-25.2), and 16.4 (8.1-27.6) to 18.0 (9.1-29.2). RHI, but not AI, remained significantly associated with CACS after risk factors adjustment. CONCLUSIONS: In this large study of coronary artery calcium and vascular function, we found an association between CACS and both endothelial dysfunction and arterial stiffness, indicating that they may reflect similar mechanisms for development of cardiovascular disease.

4.
Hypertension ; 76(5): 1616-1624, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32895017

RESUMO

Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age<-5.7 years), normal (Δ-age -5.7 to 6.8 years) and supernormal vascular aging (Δ-age>6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly (P<0.01) and inversely associated with cardiovascular events. Compared with normal vascular aging, supernormal vascular aging had lower risk (hazard ratio, 0.59 [95% CI, 0.41-0.85]), whereas early vascular aging had higher risk (hazard ratio, 2.70 [95% CI, 1.55-4.70]) of cardiovascular events, in particular coronary events. There was no significant association with all-cause mortality. This study represents the first validation of the clinical significance of the supernormal vascular aging concept, based on prospective data. Its further characterization may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.

5.
Angiology ; : 3319720946976, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762347

RESUMO

Even though abdominal aortic aneurysm (AAA) and coronary heart disease (CHD) are both related to atherosclerosis, there could be important differences in risk factors. Based on Malmö Diet and Cancer Cohort, the incidence of AAA and CHD was followed prospectively. Cox regression was used to calculate the association of each factor with AAA and CHD and hazards ratio were compared using a modified Lunn-McNeil method; 447 participants developed AAA and 3129 developed CHD. After multivariate adjustments, smoking, antihypertensive medications, lipid-lowing medications, systolic and diastolic blood pressures, apolipoprotein (Apo) A1 (inversely), ApoB, ApoB/ApoA1 ratio, total leukocyte count, neutrophil count, and neutrophil to lymphocyte ratio were associated with the risks of both AAA and CHD. When comparing risk factor profiles for the 2 diseases, smoking, diastolic blood pressure, ApoA1, and ApoB/ApoA1 ratio had stronger associations with risk of AAA than with risk of CHD, while diabetes and unmarried status showed increased risk of CHD, but not of AAA (all P values for equal association <.01). The results from this big population study confirm that the risk factor profiles for AAA and CHD show not only many similarities but also several important differences.

6.
Environ Res ; 191: 110095, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32846176

RESUMO

BACKGROUND: Long-term exposure to air pollution increases the risk of cardiovascular morbidity and mortality, but the mechanisms are not fully known. Current evidence suggests that air pollution exposure contributes to the development of atherosclerosis. There are few studies investigating associations between air pollution and carotid plaques, a well-known precursor of cardiovascular disease. METHODS: A Swedish population-based cohort (aged 45-64 years at recruitment) was randomly selected from the Malmö Diet and Cancer study between 1991 and 1994, of which 6103 participants underwent ultrasound examination of the right carotid artery to determine carotid plaque presence and carotid intima media thickness (CIMT). Participants were assigned individual residential air pollution exposure (source-specific PM2.5, PM10, NOx, BC) at recruitment from Gaussian dispersion models. Logistic and linear regression models, adjusted for potential confounders and cardiovascular risk factors, were used to investigate associations between air pollutants and prevalence of carotid plaques, and CIMT, respectively. RESULTS: The prevalence of carotid plaques was 35%. The mean levels of PM2.5 and PM10 at recruitment were 11 and 14 µg/m3, most of which was due to long range transport. The exposure contrast within the cohort was relatively low. PM2.5 exposure was associated with carotid plaques in a model including age and sex only (OR 1.10 (95% CI 1.01-1.20) per 1 µg/m3), but after adjustment for cardiovascular risk factors and socioeconomic status (SES) the association was weak and not significant (OR 1.05 (95% CI 0.96-1.16) per 1 µg/m3). The pattern was similar for PM10 and NOx exposure. Associations between air pollutants and plaques were slightly stronger for long-term residents and in younger participants with hypertension. There was no clear linear trend between air pollution exposure and plaque prevalence. Non-significant slightly positive associations were seen between air pollution exposures and CIMT. CONCLUSIONS: In this large, well-controlled cross-sectional study at low exposure levels we found no significant associations between air pollution exposures and subclinical atherosclerosis in the carotid arteries, after adjusting for cardiovascular risk factors and SES. Further epidemiological studies of air pollution and intermediate outcomes are needed to explain the link between air pollution and cardiovascular events.

7.
J Hum Hypertens ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415282

RESUMO

Different methods can be used to define healthy vascular ageing (HVA). In this prospective cohort study, we explored three different definitions in order to provide guidance for which to use. 2718 subjects were included from the Cardiovascular (CV) arm of the Malmö Diet Cancer Study (MDCS; median age 71.9 years, 62.2% females). Three different definitions of HVA were used: HVA-1 (<15th percentile of aortic pulse wave velocity (aPWV) distribution from age-quintiles); HVA-2 (<35th percentile of aPWV+ <35th percentile of carotid Intima-Media Thickness. cIMT); and HVA-3 (aPWV < 7.6 m/s + no hypertension). The HVA-1 and HVA-2 groups were compared with the HVA-3, and to the corresponding groups without HVA (non-HVA), in cross-sectional analyses for baseline characteristics and using Cox regressions for prospective risk, yielding hazard ratios (HRs) adjusted for conventional risk factors. A composite CVD endpoint was used, consisting of myocardial infarctions, ischemic heart disease mortality, and coronary artery procedures. The baseline characteristics were, with minor exceptions, similar across HVA groups. In the fully adjusted model, the HRs (95%CI) were 0.62 (0.41-0.93), 0.45 (0.26-0.76), and 0.56 (0.34-0.91) for HVA-1, HVA-2, and HVA-3, respectively. In summary, this observational study of elderly subjects provides examples of integrating hypertension and cIMT in the definition of HVA, as compared with only using aPWV. As aPWV itself is such a robust marker of HVA, it is demanding to find additional markers which improve the definition. There is a need to create a generally accepted definition of HVA.

8.
Scand J Public Health ; : 1403494820919572, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32466721

RESUMO

Aims: Worldwide, smokeless-tobacco use is a major risk factor for oral cancer. Evidence regarding the particular association between Swedish snus use and oral cancer is, however, less clear. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between snus use and oral cancer. Methods: A total of 418,369 male participants from nine cohort studies were followed up for oral cancer incidence through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. Results: During 9,201,647 person-years of observation, 628 men developed oral cancer. Compared to never-snus use, ever-snus use was not associated with oral cancer (adjusted HR 0.90, 95% CI: 0.74, 1.09). There were no clear trends in risk with duration or intensity of snus use, although lower intensity use (⩽ 4 cans/week) was associated with a reduced risk (HR 0.65, 95% CI: 0.45, 0.94). Snus use was not associated with oral cancer among never smokers (HR 0.87, 95% CI: 0.57, 1.32). Conclusions: Swedish snus use does not appear to be implicated in the development of oral cancer in men.

9.
Sci Rep ; 10(1): 7230, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350354

RESUMO

Red cell distribution width (RDW) has been suggested to have a predictive potential for several cardiovascular diseases, but its association with abdominal aortic aneurysm (AAA) is unknown. We examined whether RDW is associated with the risk of AAA among 27,260 individuals from the population-based Malmö Diet and Cancer Study cohort. Data of baseline characteristics were collected during 1991-1996. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for AAA across quartiles of RDW. During a median follow-up of 21.7 years, 491 subjects developed AAA. After adjustment for other confounding factors, participants in the highest quartile of RDW experienced 61% increased risk of AAA as compared to those with the lowest quartile (HR = 1.61, CI = 1.20, 2.12). RDW showed similar relationship with severe (i.e. ruptured or surgically repaired) AAA or non-severe AAA (adjusted HR 1.58 and 1.60, respectively). The observed association between RDW and AAA risk was significant in current smokers (adjusted HR = 1.68, CI = 1.18, 2.38) but not in former smokers (adjusted HR = 1.13, CI = 0.72, 1.79), or never-smokers (adjusted HR = 1.77, CI = 0.74, 4.22). Elevated RDW is associated with increased future incidence of AAA, however the causal and pathophysiological mechanisms remain to be explored.

10.
Arterioscler Thromb Vasc Biol ; 40(7): 1777-1786, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460577

RESUMO

OBJECTIVE: The aim of this study was to investigate if there is a causal relationship between circulating levels of TIM-1 (T-cell immunoglobulin and mucin domain 1) and incidence of stroke. Approach and Results: Plasma TIM-1 was analyzed in 4591 subjects (40% men; mean age, 57.5 years) attending the Malmö Diet and Cancer Study. Incidence of stroke was studied in relation to TIM-1 levels during a mean of 19.5 years follow-up. Genetic variants associated with TIM-1 (pQTLs [protein quantitative trait loci]) were examined, and a 2-sample Mendelian randomization analysis was performed to explore the role of TIM-1 in stroke using summary statistics from our pQTLs and the MEGASTROKE consortium. A total of 416 stroke events occurred during follow-up, of which 338 were ischemic strokes. After risk factor adjustment, TIM-1 was associated with increased incidence of all-cause stroke (hazards ratio for third versus first tertile, 1.44 [95% CI, 1.10-1.87]; P for trend, 0.004), and ischemic stroke (hazards ratio, 1.42 [95% CI, 1.06-1.90]; P for trend, 0.011). Nineteen independent lead SNPs, located in three genomic risk loci showed significant associations with TIM-1 (P<5×10-8). A 2-sample Mendelian Randomization analysis suggested a causal effect of TIM-1 on stroke (ß=0.083, P=0.0004) and ischemic stroke (ß=0.102, P=7.7×10-5). CONCLUSIONS: Plasma level of TIM-1 is associated with incidence of stroke. The genetic analyses suggest that this could be a causal relationship.


Assuntos
Receptor Celular 1 do Vírus da Hepatite A/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Biomarcadores/sangue , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Receptor Celular 1 do Vírus da Hepatite A/sangue , Humanos , Incidência , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Prospectivos , Locos de Características Quantitativas , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Suécia/epidemiologia , Fatores de Tempo
11.
ESC Heart Fail ; 7(4): 1891-1899, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32410391

RESUMO

AIMS: Hypertension is the leading cause for the development of heart failure (HF). Here, we aimed to identify cardiomyocyte stretch-induced circulating biomarkers for predicting hypertension-associated HF. METHODS AND RESULTS: Circulating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4742 individuals from the Malmö Diet and Cancer study. Protein levels were compared with stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVMs) in response to 1-48 h of mechanical stretch. We also studied the association between protein levels and hypertension and HF incidence using respectively binary logistic and Cox regressions. Levels of 35 proteins were differentially expressed after Bonferroni correction in incident HF vs. control (P < 3.4E-4). Growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), IL-1 receptor type 1, and urokinase plasminogen activator surface receptor had corresponding mRNA levels up-regulated by stretch in NRVMs at all time points (P < 0.05). These four proteins were individually associated with increased risk of HF after age and sex adjustment [hazard ratio (HR) per standard deviation: 1.19 ≤ HR ≤ 1.49, P ≤ 4.90E-3]. GDF-15 and IL-6 were associated with HF independently of each other (1.22 ≤ HR ≤ 1.33, P ≤ 0.001). In subjects with hypertension, these associations remained significant after further adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (1.23 ≤ HR ≤ 1.45, P ≤ 0.001). A higher fasting value of a GDF-15, IL-6 score aggregate was associated with increased risk of hypertensive HF after adjustment for all traditional risk factors for HF and NT-proBNP (HR = 1.31, P = 2.19E-4). CONCLUSIONS: Cardiomyocyte mRNA levels of GDF-15 and IL-6 are consistently up-regulated by stretch, and their circulating protein levels predict HF in hypertensive subjects independently of NT-proBNP during long-term follow-up. Our results encourage further studies on lower blood pressure goals in hypertensive subjects with high GDF-15 and IL-6, and interventions targeted at stretch-induced cardiomyocyte expressed biomarkers.

12.
BMC Nephrol ; 21(1): 124, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268898

RESUMO

BACKGROUND: Although the prevalence of kidney disease is higher in those with reduced lung function, the longitudinal relationship between low lung function and future risk of chronic kidney disease (CKD) has not been widely explored. METHODS: Baseline lung function was assessed in 20,700 men and 7325 women from 1974 to 1992. Mean age was 43.4 (±6.6) and 47.5 (±7.9) for men and women respectively. Sex-specific quartiles of FEV1 and FVC (L) were created (Q4: highest, reference) and the cohort was also divided by the FEV1/FVC ratio (≥ or < 0.70). Cox proportional hazards regression was used to determine the risk of incident CKD events (inpatient or outpatient hospital diagnosis of CKD) in relation to baseline lung function after adjustment for various confounding factors. RESULTS: Over 41 years of follow-up there were 710 and 165 incident CKD events (main diagnosis) in men and women respectively. Low FEV1 was strongly associated with future risk of CKD in men (Q1 vs Q4 adjusted HR: 1.46 (CI:1.14-1.89), p-trend 0.002). Similar findings were observed for FVC in men (1.51 (CI:1.16-1.95), p-trend 0.001). The adjusted risks were not found to be significant in women, for either FEV1 or FVC. FEV1/FVC < 0.70 was not associated with increased incidence of CKD in men or women. CONCLUSION: Low FEV1 and FVC levels at baseline are a risk factor for the development of future incident CKD in men. Monitoring kidney function in those with reduced vital capacity in early life could help with identifying those at increased risk of future CKD.

13.
Eur Respir J ; 56(2)2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32341107

RESUMO

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO GLI LLN but GLI LLN but GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for D LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

14.
Eur J Prev Cardiol ; : 2047487320909300, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126830

RESUMO

BACKGROUND: It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. DESIGN: The design of this study was as a cross-sectional analysis from a population-based study cohort. METHODS: From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. RESULTS: Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score >0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score >0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have >1 carotid plaques (1.67 (1.61-1.74)). CONCLUSION: Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.

15.
Am J Phys Med Rehabil ; 99(6): 522-531, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32167960

RESUMO

OBJECTIVE: The aim of the study was to present the methodology, cohort demographics, and initial results of the Swedish SPinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA). DESIGN: The SPICA is based on the Swedish CArdioPulmonary BioImage Study, a study on cardiopulmonary diseases in a cohort of 30,000 people. The assessments in the SPICA cover the structure and function of the cardiopulmonary and autonomic systems using bioimaging and functional analyses, together with a study-specific questionnaire and generic and spinal cord injury-specific assessment tools. The inclusion criteria were as follows: age 50-65 yrs, traumatic spinal cord injury of 5 yrs or more, and injury levels C1-T6, American Spinal Injury Association Impairment Scale A-C. RESULTS: Of 38 potential participants, 25 comprised the final sample (20% women, mean age 58 yrs, mean time since injury 28 yrs). Eight percent had sustained a cardiovascular event, and 72% were classified as a high risk for cardiovascular disease. Asthma was previously diagnosed in only 8%, and none had chronic obstructive pulmonary disease. CONCLUSIONS: The risk for cardiovascular disease in people with severe high-level spinal cord injury is a major clinical concern. Forthcoming studies in the SPICA will provide new knowledge of cardiopulmonary health in this cohort, which can guide future research and be used to develop long-term management.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Doenças Cardiovasculares/etiologia , Traumatismos da Medula Espinal/complicações , Idoso , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Traumatismos da Medula Espinal/fisiopatologia , Suécia/epidemiologia
16.
J Diabetes Complications ; 34(5): 107551, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32061519

RESUMO

AIMS: The aim of the present study was to compare outcomes of endovascular surgery versus open vascular surgery in patients with diabetic foot ulcer (DFU) and peripheral arterial disease (PAD). METHODS: Between 1984 and 2006, 1151 patients with DFU were admitted to the diabetic foot care team. Three hundred seventy-six patients with 408 limbs were consecutively included at a multidisciplinary foot center, 289 limbs were treated with endovascular surgery and 119 limbs with open vascular surgery first strategy. A propensity score adjusted analysis was performed to compare outcomes for type of revascularization. RESULTS: Major amputation rates at 3 years were 17.0% and 16.8% (p = 0.97) and mortality at 3 years were 43.1% and 46.5% (p = 0.55) after endovascular surgery and open vascular surgery, respectively. In the propensity score adjusted analysis, patients undergoing endovascular surgery first had similar outcomes in terms of major amputation, mortality, combined major amputation/mortality compared to those undergoing open vascular surgery. Longer time to intervention (p = 0.003) was associated with increased major amputation rate in the multivariable Cox regression analysis. CONCLUSION: The endovascular surgery first and open vascular surgery first strategies were associated with similar long-term results in a large cohort of patients with DFU and PAD undergoing revascularization. Rapid revascularization reduces the risk of amputation.

17.
Eur Heart J ; 41(28): 2632-2640, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32090257

RESUMO

AIM: To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort. METHODS AND RESULTS: We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82-0.93, P-trend < 0.001), dietary fibre (per 10 g/day, 0.77; 0.69-0.86, P-trend < 0.001), milk (per 200 g/day, 0.95; 0.91-0.99, P-trend = 0.02), yogurt (per 100 g/day, 0.91; 0.85-0.97, P-trend = 0.004), and cheese (per 30 g/day, 0.88; 0.81-0.97, P-trend = 0.008), while higher risk was observed with higher red meat consumption which attenuated when adjusted for the other statistically significant foods (per 50 g/day, 1.07; 0.96-1.20, P-trend = 0.20). For haemorrhagic stroke (1430 cases), higher risk was associated with higher egg consumption (per 20 g/day, 1.25; 1.09-1.43, P-trend = 0.002). CONCLUSION: Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.

18.
J Am Heart Assoc ; 9(3): e014132, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32009521

RESUMO

Background It remains unclear whether heritable factors can contribute to risk stratification for ischemic stroke in patients with atrial fibrillation (AF). We examined whether having a sibling with ischemic stroke was associated with increased risk of ischemic stroke and mortality in patients with AF. Methods and Results In this nationwide study of the Swedish population, patients with AF and their siblings were identified from the Swedish patient registers and the Swedish MGR (Multi-Generation Register). Ischemic stroke events were retrieved from the Swedish patient registers and CDR (Cause of Death Register). Risk of ischemic stroke was compared between patients with AF with and without a sibling affected by ischemic stroke, AF, or both ischemic stroke and AF. The total study population comprised 113 988 subjects (mean age, 60±12 years) diagnosed with AF between 1989 and 2012. In total, 11 709 of them were diagnosed with a first ischemic stroke and 20 097 died during a mean follow-up time of 5.5 years for ischemic stroke and 5.9 years for mortality. After adjustment for covariates having a sibling with ischemic stroke, or both ischemic stroke and AF, was associated with increased risk of ischemic stroke (hazard ratio, 1.31; 95% CI, 1.23-1.40 or hazard ratio, 1.36; 95% CI, 1.24-1.49, respectively). Furthermore, ischemic stroke in a sibling was associated with all-cause mortality (hazard ratio, 1.09; 95% CI, 1.05-1.14). In contrast, the risk of stroke was only marginally increased for patients with AF with a spouse affected by ischemic stroke. Conclusions Having a sibling affected by ischemic stroke confers an increased risk of ischemic stroke and death independently of traditional risk factors in patients with AF.

19.
Atherosclerosis ; 295: 25-30, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31981948

RESUMO

BACKGROUND AND AIMS: Genetic loci associated with CHD show different relationships with intima-media thickness in the common carotid artery (IMT-CCA) and in the bulb (IMT-bulb). We evaluated if IMT-CCA and IMT-bulb differ also with respect to circulating protein profiles and risk of incident atherosclerotic disease. METHODS: In three Swedish cohorts (MDC, IMPROVE, PIVUS, total n > 7000), IMT-CCA and IMT-bulb were assessed by ultrasound at baseline, and 86 cardiovascular-related proteins were analyzed. In the PIVUS study only, IMT-CCA and IMT-bulb were investigated in relation to incident atherosclerotic disease over 10 years of follow-up. RESULTS: In a meta-analysis of the analysis performed separately in the cohorts, three proteins, matrix metalloproteinase-12 (MMP-12), hepatocyte growth factor (HGF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were associated with IMT-CCA when adjusted for traditional cardiovascular risk factors. Five proteins were associated with IMT-bulb (MMP-12, growth/differentiation factor 15 (GDF-15), osteoprotegerin, growth hormone and renin). Following adjustment for cardiovascular risk factors, IMT-bulb was significantly more closely related to incident stroke or myocardial infarction (total number of cases, 111) than IMT-CCA in the PIVUS study (HR 1.51 for 1 SD, 95%CI 1.21-1.87, p < 0.001 vs HR 1.17, 95%CI 0.93-1.47, p = 0.16). MMP-12 levels were related to this combined end-point (HR 1.30, 95%CI 1.08-1.56, p = 0.0061). CONCLUSIONS: Elevated levels of MMP-12 were associated with both IMT-CCA and IMT-bulb, but other proteins were significantly related to IMT in only one of these locations. The finding that IMT-bulb was more closely related to incident atherosclerotic disease than IMT-CCA emphasizes a difference between these measurements of IMT.

20.
Nat Commun ; 11(1): 163, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919418

RESUMO

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.


Assuntos
Fibrilação Atrial/genética , Cardiomiopatias/genética , Doença da Artéria Coronariana/genética , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Função Ventricular Esquerda/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Cardiomiopatias/patologia , Proteínas de Transporte/genética , Estudos de Casos e Controles , Inibidor de Quinase Dependente de Ciclina p21/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Proteínas dos Microfilamentos/genética , Proteínas Musculares/genética , Fatores de Risco
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