Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 548
Filtrar
1.
Hypertension ; : HYPERTENSIONAHA12016711, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33550821

RESUMO

A lower day-to-night systolic blood pressure (BP) dip has previously been associated with poor brain health and cognitive functions. Here, we sought to examine whether reduced (nighttime/daytime ratio of systolic BP >0.9 and ≤1) and reverse (nighttime/daytime ratio of systolic BP >1) dipping of systolic BP is associated with the prospective risk of being diagnosed with any dementia in Swedish older men. Twenty-four-hour ambulatory BP monitoring was used to estimate the nocturnal systolic BP dipping status of men at mean age 71 (n=997; 35% on antihypertensive medication) and 77.6 (n=611; 41% on antihypertensive medication). Dementia incidence during the observational period up to 24 years (n=286 cases) was determined by reviewing participants' medical history and independently confirmed by at least 2 experienced geriatricians. Using time-updated Cox regression (ie, time-updated information on covariates and exposure), we found that reverse systolic BP dipping was associated with a higher risk of being diagnosed with any dementia (adjusted HR, 1.64 [95% CI, 1.14-2.34], P=0.007) and Alzheimer's disease (1.67 [1.01-2.76], P=0.047) but not vascular dementia (1.29 [0.55-3.06], P=0.559). In contrast, reduced dipping of nocturnal systolic BP was not associated with a higher risk of being diagnosed with dementia. Our findings suggest that reverse systolic BP dipping may represent an independent risk factor for dementia and Alzheimer's disease in older men. Future studies should decipher whether therapies lowering nocturnal systolic BP below daytime levels, such as bedtime dosing of antihypertensive medication, can meaningfully curb the development of dementia.

2.
Sci Rep ; 11(1): 2978, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536506

RESUMO

The impact of most, but not all, cardiovascular risk factors decline by age. We investigated how the metabolic syndrome (MetS) was related to cardiovascular disease (CVD) during 40 years follow-up in the Uppsala Longitudinal Study of Adult Men (ULSAM, 2,123 men all aged 50 at baseline with reinvestigations at age 60, 70, 77 and 82). The strength of MetS as a risk factor of incident combined end-point of three outcomes (CVD) declined with ageing, as well as for myocardial infarction, ischemic stroke and heart failure when analysed separately. For CVD, the risk ratio declined from 2.77 (95% CI 1.90-4.05) at age 50 to 1.30 (95% CI 1.05-1.60) at age 82. In conclusion, the strength of MetS as a risk factor of incident CVD declined with age. Since MetS was significantly related to incident CVD also at old age, our findings suggest that the occurrence of MetS in the elderly should not be regarded as innocent. However, since our data were derived in an observational study, any impact of MetS in the elderly needs to be verified in a randomized clinical intervention trial.

3.
J Am Heart Assoc ; 10(2): e017579, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33399003

RESUMO

Background The molecular mechanisms involved in atrial fibrillation are not well known. We used plasma metabolomics to investigate if we could identify novel biomarkers and pathophysiological pathways of incident atrial fibrillation. Methods and Results We identified 200 endogenous metabolites in plasma/serum by nontargeted ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry in 3 independent population-based samples (TwinGene, n=1935, mean age 68, 43% females; PIVUS [Prospective Investigation of the Vasculature in Uppsala Seniors], n=897, mean age 70, 51% females; and ULSAM [Uppsala Longitudinal Study of Adult Men], n=1118, mean age 71, all males), with available data on incident atrial fibrillation during 10 to 12 years of follow-up. A meta-analysis of ULSAM and PIVUS was used as a discovery sample and TwinGene was used for validation. In PIVUS, we also investigated associations between metabolites of interest and echocardiographic indices of myocardial geometry and function. Genome-wide association studies were performed in all 3 cohorts for metabolites of interest. In the meta-analysis of PIVUS and ULSAM with 430 incident cases, 4 metabolites were associated with incident atrial fibrillation at a false discovery rate <5%. Of those, only 9-decenoylcarnitine was associated with incident atrial fibrillation and replicated in the TwinGene sample (288 cases) following adjustment for traditional risk factors (hazard ratio, 1.24 per unit; 95% CI, 1.06-1.45, P=0.0061). A meta-analysis of all 3 cohorts disclosed another 4 significant metabolites. In PIVUS, 9-decenoylcarnitine was related to left atrium size and left ventricular mass. A Mendelian randomization analysis did not suggest a causal role of 9-decenoylcarnitine in atrial fibrillation. Conclusions A nontargeted metabolomics analysis disclosed 1 novel replicated biomarker for atrial fibrillation, 9-Decenoylcarnitine, but this acetylcarnitine is likely not causally related to atrial fibrillation.

4.
Hypertension ; 77(1): 39-48, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33296250

RESUMO

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.

5.
Respir Med ; 176: 106282, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310204

RESUMO

BACKGROUND: Underlying mechanism leading to impaired lung function are incompletely understood. OBJECTIVES: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function. METHODS: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV1%) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality. MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis, 22 proteins were associated with lower FEV1% in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV1%. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV1% per standard deviation of protein level -1.4, (95% CI, -2.5 to -0.3) for GDF-15, and -0.8, (95% CI, -1.5 to -0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV1%. CONCLUSIONS: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.

6.
Lipids Health Dis ; 19(1): 249, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287856

RESUMO

BACKGROUND: Lipoproteins at aberrant levels are known to play a role in cardiovascular disease. The metabolite of the insecticide dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), physically associates with lipids and accumulates in adipose tissue. Little is known about which lipoproteins associate with p,p'-DDE. An association between p,p'-DDE exposure and altered levels of circulating lipids was assessed in a large human cohort using a detailed analysis of lipoprotein content. METHODS: Plasma samples were collected from the subset of 75-year old Swedes in the Prospective Investigation of the Vasculature of Uppsala Seniors (PIVUS) cohort who were not prescribed lipid lowering medication (n = 571). p,p'-DDE concentrations in plasma were measured using high-throughput solid phase extraction and gas chromatography-high resolution mass spectrometry. Analysis of plasma lipoprotein content was performed with nuclear magnetic resonance spectroscopy. RESULTS: Detectable levels of p,p'-DDE were found in the plasma samples of all subjects. Elevated p,p'-DDE levels were associated with increased concentrations of lipoproteins of all diameters, with the exception of high density lipoprotein (HDL) of diameters between 14.3 nm-10.9 nm. Of the lipoprotein constituents, triglycerides were most uniformly associated with elevated p,p'-DDE across lipoproteins. p,p'-DDE was furthermore associated with apolipoprotein B, but not apolipoprotein A1. CONCLUSIONS: The positive associations observed between each lipoprotein class and elevated p,p'-DDE support previous data suggesting that p,p'-DDE interacts with lipoproteins within plasma. It is speculated that both physio-chemical and biological mechanisms may explain why p,p'-DDE does not uniformly associate with lipids across lipoproteins.

7.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33263030

RESUMO

Study objectives: Obesity is often associated with lower lung function; however, the interaction of lung function with central obesity and physical inactivity is less clear. As such, we investigated the effect on lung function of body size (body mass index (BMI)), central obesity (waist circumference (WC)) and self-reported physical activity. Methods: Lung function, height, weight and WC were measured in 22 743 participants (12 791 women), aged 45-75 years, from the EpiHealth cohort study. Physical activity, gender and educational level were assessed using a questionnaire. Results: Obesity, central obesity and physical inactivity were all associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). However, in participants without central obesity there was an increase in both FEV1 and FVC by BMI (% predicted FVC increasing from median 98%, interquartile range (IQR) 89-110% in underweight participants (BMI <20) to 103%, IQR 94-113% in obese participants (BMI ≥30)). In contrast, there was a decrease in % predicted FVC in participants with central obesity (from 98%, IQR 89-109% in the normal weight group to 95%, IQR 85-105% in the obese weight group). We further found a negative association between physical activity and lung function among those with low and high levels of physical activity (% predicted FEV1 97%, IQR 86-107% versus 103%, IQR 94-113%, respectively and % predicted FVC 96%, IQR 85-106% versus 103%, IQR 94-113%, respectively). All results remained when calculated by z-scores. Conclusions: The association between BMI and lung function is dependent on the presence of central obesity. Independent of obesity, there is an association between physical activity and lung function.

8.
PLoS One ; 15(11): e0241558, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152050

RESUMO

BACKGROUND: The normal ranges for clinical chemistry tests are usually defined by cut-offs given by the distribution in healthy individuals. This approach does however not indicate if individuals outside the normal range are more prone to disease. METHODS: We studied the associations and risk prediction of 11 plasma and serum biomarkers with all-cause mortality in two population-based cohorts: a Swedish cohort (X69) initiated in 1969, and the UK Biobank (UKB) initiated in 2006-2010, with up to 48- and 9-years follow-up, respectively. RESULTS: In X69 and in UKB, 18,529 and 425,264 individuals were investigated, respectively. During the follow-up time, 14,475 deaths occurred in X69 and 17,116 in UKB. All evaluated tests were associated with mortality in X69 (P<0.0001, except bilirubin P<0.005). For calcium, blood urea nitrogen, bilirubin, hematocrit, uric acid, and iron, U-shaped associations were seen (P<0.0001). For leukocyte count, gamma-glutamyl transferase, alkaline phosphatases and lactate dehydrogenase, linear positive associations were seen, while for albumin the association was negative. Similar associations were seen in UKB. Addition of all biomarkers to a model with classical risk factors improved mortality prediction (delta C-statistics: +0.009 in X69 and +0.023 in UKB, P<0.00001 in both cohorts). CONCLUSIONS: Commonly used clinical chemistry tests were associated with all-cause mortality both in the medium- and long-term perspective, and improved mortality prediction beyond classical risk factors. Since both linear and U-shaped relationships were found, we propose to define the normal range of a clinical chemistry test based on its association with mortality, rather than from the distribution.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33153859

RESUMO

BACKGROUND AND AIMS: An increased amount of visceral adipose tissues has been related to atherosclerosis and future cardiovascular events. The present study aims to investigate how the abdominal fat distribution links to plasma levels of cardiovascular-related proteins. METHOD AND RESULTS: In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 326, all aged 50 years), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue volumes were quantified by MRI. Eighty-six cardiovascular-related proteins were measured by the proximity extension assay (PEA). Similar investigations were carried out in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 400, all aged 75 years). In the discovery dataset (POEM), 10 proteins were related to the VAT/SAT-ratio using false discovery rate <.05. Of those, Cathepsin D (CTSD), Interleukin-1 receptor antagonist protein (IL-1RA) and Growth hormone (GH) (inversely) were related to the VAT/SAT-ratio in the validation in PIVUS following adjustment for sex, BMI, smoking, education level and exercise habits (p < 0.05). In a secondary analysis, a meta-analysis of the two samples suggested that 15 proteins could be linked to the VAT/SAT-ratio following adjustment as above and Bonferroni-correction of the p-value. CONCLUSION: Three cardiovascular-related proteins, cathepsin D, IL-1RA and growth hormone, were being associated with the distribution of abdominal adipose tissue using a discovery/validation approach. A meta-analysis of the two samples suggested that also a number of other cardiovascular-related proteins could be associated with an unfavorable abdominal fat distribution.

10.
Nat Metab ; 2(10): 1135-1148, 2020 10.
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.

11.
J Lipid Atheroscler ; 9(3): 334-348, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33024729

RESUMO

The term persistent organic pollutants (POPs) denotes chemicals with known or suspected adverse health effects in animals or humans and with chemical properties that make them accumulate in the environment, including animals or humans. Lipid-soluble POPs, like dioxins, polychlorinated biphenyls (PCBs) and organochlorine pesticides are transported by lipoproteins and accumulate in adipose tissue. High levels of these compounds in the circulation have been associated with elevated cholesterol and triglycerides in cross-sectional studies and with an increase in mainly low-density lipoprotein cholesterol in a longitudinal study. Also, non-lipid-soluble POPs, such as perfluoroalkyl substances (PFASs) compounds have been associated with increased total cholesterol levels. Carotid artery atherosclerosis has been related to elevated levels of mainly highly chlorinated PCBs and to highly fluorinated PFASs, but in this case only in women. Both cross-sectional and prospective studies have shown dioxins, PCBs, as well as PFASs to be linked to cardiovascular disease (CVD) and mortality. In conclusion, as highlighted in this review, several lines of evidence support the view that POPs of different chemical classes could be linked to lipid abnormalities, carotid atherosclerosis and overt CVD like myocardial infarction and stroke.

12.
Sci Rep ; 10(1): 16474, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020500

RESUMO

Better risk prediction and new molecular targets are key priorities in type 2 diabetes (T2D) research. Little is known about the role of the urine metabolome in predicting the risk of T2D. We aimed to use non-targeted urine metabolomics to discover biomarkers and improve risk prediction for T2D. Urine samples from two community cohorts of 1,424 adults were analyzed by ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). In a discovery/replication design, three out of 62 annotated metabolites were associated with prevalent T2D, notably lower urine levels of 3-hydroxyundecanoyl-carnitine. In participants without diabetes at baseline, LASSO regression in the training set selected six metabolites that improved prediction of T2D beyond established risk factors risk over up to 12 years' follow-up in the test sample, from C-statistic 0.866 to 0.892. Our results in one of the largest non-targeted urinary metabolomics study to date demonstrate the role of the urine metabolome in identifying at-risk persons for T2D and suggest urine 3-hydroxyundecanoyl-carnitine as a biomarker candidate.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33123723

RESUMO

CONTEXT: Metabolic differences between ectopic fat depots may provide novel insights to obesity-related diseases. OBJECTIVE: To investigate the plasma metabolomic profiles in relation to visceral adipose tissue (VAT) volume and liver and pancreas fat percentages. DESIGN: Cross-sectional. SETTING: Multicenter at academic research laboratories. PATIENTS: Magnetic resonance imaging (MRI) was used to assess VAT volume, the percentage of fat in the liver and pancreas (proton density fat fraction [PDFF]) at baseline in 310 individuals with a body mass index ≥ 25 kg/m2 and with serum triglycerides ≥ 1.7 mmol/l and/or type 2 diabetes screened for inclusion in the 2 effect of omega-3 carboxylic acid on liver fat content studies. INTERVENTION: None. MAIN OUTCOME MEASURE: Metabolomic profiling with mass spectroscopy enabled the determination of 1063 plasma metabolites. RESULTS: Thirty metabolites were associated with VAT volume, 31 with liver PDFF, and 2 with pancreas PDFF when adjusting for age, sex, total body fat mass, and fasting glucose. Liver PDFF and VAT shared 4 metabolites, while the 2 metabolites related to pancreas PDFF were unique. The top metabolites associated with liver PDFF were palmitoyl-palmitoleoyl-GPC (16:0/16:1), dihydrosphingomyelin (d18:0/22:0), and betaine. The addition of these metabolites to the Liver Fat Score improved C-statistics significantly (from 0.776 to 0.861, P = 0.0004), regarding discrimination of liver steatosis. CONCLUSION: Liver PDFF and VAT adipose tissue shared several metabolic associations, while those were not shared with pancreatic PDFF, indicating partly distinct metabolic profiles associated with different ectopic fat depots. The addition of 3 metabolites to the Liver Fat Score improved the prediction of liver steatosis.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32889544

RESUMO

OBJECTIVES: Clinical presentation of primary Sjögren's syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. METHODS: We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. RESULTS: We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10-62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. CONCLUSION: Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.

15.
Sci Rep ; 10(1): 13355, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32770136

RESUMO

Chronically blunted nocturnal blood pressure (BP) dipping has been shown to increase the future risk of cardiovascular diseases. In the present cross-sectional study, we investigated whether self-reported insomnia symptoms were associated with an altered 24-h BP profile and blunted nocturnal BP dipping (night-to-day BP ratio > 0.90) in older men. For the analysis, we used 24-h ambulatory blood pressure data and reports of insomnia symptoms (difficulty initiating sleep, DIS; and early morning awakenings, EMA) from 995 Swedish men (mean age: 71 years). Compared to men without DIS, those reporting DIS (10% of the cohort) had a higher odds ratio of diastolic non-dipping (1.85 [1.15, 2.98], P = 0.011). Similarly, men who reported EMA (19% of the cohort) had a higher odds ratio of diastolic non-dipping than those without EMA (1.57 [1.09, 2.26], P = 0.015). Despite a slightly higher nocturnal diastolic BP among men with EMA vs. those without EMA (+ 1.4 mmHg, P = 0.042), no other statistically significant differences in BP and heart rate were found between men with and those without insomnia symptoms. Our findings suggest that older men reporting difficulty initiating sleep or early morning awakenings may have a higher risk of nocturnal diastolic non-dipping. Our findings must be replicated in larger cohorts that also include women.

16.
Atherosclerosis ; (307): 11-15, Aug., 2020. tab.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1122622

RESUMO

BACKGROUND AND AIMS: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. METHODS: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. RESULTS: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 ± 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean ± SD change of 2.9 ± 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p < 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). CONCLUSIONS: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.


Assuntos
Biomarcadores , Doenças Cardiovasculares , Insuficiência Renal Crônica , Proteômica
17.
Blood Press ; 29(6): 370-374, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32603237

RESUMO

PURPOSE: Early treatment of hypertension is important to reduce adverse cardiovascular outcomes. The aim of this study was to investigate the time delay from detection of a high blood pressure in a health screening survey to hypertension diagnosis in primary care. MATERIALS AND METHODS: Seventy years old inhabitants in the Uppsala County were randomly invited to the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. We found 409 individuals without antihypertensive treatment with a blood pressure >140/90 mmHg, being the average of three recordings measured after 30 min rest in a supine position. These individuals were recommended to ask their primary care physician to further investigate this finding. RESULTS: During 10 years of follow-up, 285 of them (70%) received a hypertension diagnosis. The mean time to diagnosis was 5 (SD 2) years. The chance of receiving a diagnosis of hypertension during the follow-up period in this group with elevated blood pressure at baseline was related to the systolic blood pressure (OR 1.04 per 1 mmHg, 95%CI 1.02-1.04), the BMI (OR 1.06 per 1 kg/m2, 95%CI 1.01-1.12), and statin use (OR 3.76, 95%CI 1.35-10.3) at the health survey, but was not significantly related to sex, prevalence of diabetes, or use of salicylic acid. No significant interaction between sex and systolic blood pressure regarding hypertension diagnosis was observed. CONCLUSION: In conclusion, when an elevated blood pressure was discovered in elderly persons at a health screening, 70% of those received a hypertension diagnosis within 10 years, with a mean time to diagnosis of 5 years. Health care actions should be enforced to shorten this time lag both in terms of information to the individuals, as well as the handling of this patient group in primary care.

18.
Atherosclerosis ; 306: 6-10, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32668293

RESUMO

BACKGROUND AND AIMS: Randomized clinical trials (RCT) have shown statin treatment to slow down the increase in carotid artery intima-media thickness (IMT) seen with ageing. However, those RCTs usually have a limited follow-up (1-3 years). Here an observational study was used to investigate the real-life effect of new statin treatment over a 10-year follow-up. METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 954 individuals all aged 70 years at baseline were investigated regarding carotid artery IMT three times during 10 years (n = 771 at age 75, and n = 591 at age 80). RESULTS: At age 70, 503 subjects were statin-naïve and did not receive statin during the 10-year follow-up period (the never-statin group), while 197 subjects were statin-naïve but received statins during the follow-up period (the received-statin group). Low-density lipoprotein (LDL)-cholesterol increased over time in the never-statin group (+0.1 mmol/l, p = 0.0012), but decreased in the group receiving statin treatment (-1.1 mmol/l, p < 0.0001). The never-statin group increased significantly in IMT over the 10 years (+0.07 mm, p < 0.0001), while the numerical increase seen in the received-statin group was not significant (+0.02 mm, p = 0.22) A significant difference in the change in IMT over time was seen between the received-statin group and the never-statin group (p < 0.0001 for interaction between time and group, adjusted for a propensity score). CONCLUSIONS: This real-life observational study showed that new statin treatment reduced the increase in IMT seen over 10 years compared to subjects not treated with statins.

19.
Atherosclerosis ; 307: 11-15, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702535

RESUMO

BACKGROUND AND AIMS: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. METHODS: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. RESULTS: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 ± 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean ± SD change of 2.9 ± 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p < 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). CONCLUSIONS: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.

20.
World J Hepatol ; 12(4): 149-159, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32685107

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common disorder, with an estimated prevalence ranging from 20% to 35% in the general population. Several scores based on easily measurable biochemical and clinical parameters, including the fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), and NAFLD liver fat score (LFS), have been developed for the detection of NAFLD. However, comparative information regarding the efficacy of these scores for predicting NAFLD in population-based samples comprising normal and high-risk individuals is lacking. AIM: To evaluate four NAFLD detection scores in two samples with different NAFLD risks. METHODS: NAFLD screening was performed in a population-based sample of 50-year-old individuals in Uppsala, Sweden [n = 310; Prospective investigation of obesity, energy and metabolism (POEM) study] and a high-risk population comprising patients with a body mass index > 25 kg/m2 and either high plasma triglycerides (≥ 1.7 mmol/L) or type 2 diabetes (n = 310; EFFECT studies). NAFLD was defined as liver fat > 5.5% using magnetic resonance imaging-proton density fat fraction. FLI, HSI, LAP, and NAFLD LFS were assessed. A logistic regression model was used to evaluate the effectiveness of the different scores. RESULTS: The prevalence of NAFLD was 23% in POEM. FLI showed the highest receiver operating characteristic area under the curve (ROC AUC; 0.82) and was significantly better than the LAP score (P = 0.005 vs LAP, P = 0.08 vs LFS, P = 0.12 vs HSI) for detection of NAFLD. The other three indices performed equally in POEM (0.77-0.78). The prevalence of NAFLD was 74% in EFFECT; LFS performed best (ROC AUC 0.80) in this sample. The ROC AUC for LFS (0.80) was significantly higher than that for FLI (P = 0.0019) and LAP (P = 0.0022), but not HSI (P = 0.11). We performed a sensitivity analysis with stratification for the two high-risk subgroups (patients with diabetes or hypertriglyceridemia) from the EFFECT studies. LAP performed best in patients with hypertriglyceridemia. No major differences were observed between the other scores. CONCLUSION: The four investigated NAFLD scores performed differently in the populationbased vs high-risk setting. FLI was preferable in the population-based setting, while LFS performed best in the high-risk setting.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA