4,734 research outputs found

    Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis

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    BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ‚Čą0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death

    Prognosis and Personalized In Silico Prediction of Treatment Efficacy in Cardiovascular and Chronic Kidney Disease: A Proof-of-Concept Study

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    (1) Background: Kidney and cardiovascular diseases are responsible for a large fraction of population morbidity and mortality. Early, targeted, personalized intervention represents the ideal approach to cope with this challenge. Proteomic/peptidomic changes are largely responsible for the onset and progression of these diseases and should hold information about the optimal means of treatment and prevention. (2) Methods: We investigated the prediction of renal or cardiovascular events using previously defined urinary peptidomic classifiers CKD273, HF2, and CAD160 in a cohort of 5585 subjects, in a retrospective study. (3) Results: We have demonstrated a highly significant prediction of events, with an HR of 2.59, 1.71, and 4.12 for HF, CAD, and CKD, respectively. We applied in silico treatment, implementing on each patient’s urinary profile changes to the classifiers corresponding to exactly defined peptide abundance changes, following commonly used interventions (MRA, SGLT2i, DPP4i, ARB, GLP1RA, olive oil, and exercise), as defined in previous studies. Applying the proteomic classifiers after the in silico treatment indicated the individual benefits of specific interventions on a personalized level. (4) Conclusions: The in silico evaluation may provide information on the future impact of specific drugs and interventions on endpoints, opening the door to a precision-based medicine approach. An investigation into the extent of the benefit of this approach in a prospective clinical trial is warranted

    Diminishing benefits of urban living for children and adolescents’ growth and development

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    Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1‚Äď6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5‚Äď19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m‚Äď2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

    Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

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    Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

    Effect of Spironolactone on QRS Duration in Patients at Risk for Heart Failure (from the HOMAGE Trial)

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    The QRS duration can be easily obtained from a 12-lead electrocardiogram. Increased QRS duration reflects greater ventricular activation times and often ventricular dyssynchrony. Dyssynchrony causes an impairment of the global cardiac function and adversely affects the prognosis of patients with heart failure (HF). Little is known about the impact of pharmacologic therapies on the QRS duration, particularly for patients with presymptomatic HF with a preserved left ventricular (LV) ejection fraction (i.e., stage B HF with preserved ejection fraction [HFpEF]). The HOMAGE (Heart OMics in AGEing) trial enrolled patients at risk factors for developing HF and assigned them to receive either spironolactone or the usual care for approximately 9 months in a randomized manner. This analysis reports the effect of spironolactone on the QRS duration. A total of 525 patients was included in the analysis. The median (percentile25-75) QRS duration at baseline was 92 (84 to 106) ms. Spironolactone reduced the QRS duration at month 9 by ‚ąí2.8, 95% confidence interval ‚ąí4.6 to ‚ąí1.0 ms, p = 0.003. No significant associations were found between month 9 changes in the QRS duration and corresponding changes in the LV ejection fraction, LV mass, LV end-diastolic volume, blood pressure, N-terminal pro-brain natriuretic peptide, and procollagen type I carboxy-terminal propeptide (all p >0.05). This analysis shows that for patients with stage B HFpEF, therapy with spironolactone for 9 months shortened the QRS duration, an effect that was not associated with reductions in LV mass or volume, supporting the hypothesis that spironolactone has direct beneficial effects to improve myocardial electrical activation in patients with stage B HFpEF

    Blood pressure and cardiovascular risk in relation to birth weight and urinary sodium: An individual-participant meta-Analysis of European family-based population studies

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    Background: Although the relation of salt intake with blood pressure (BP) is linear, it is U- shaped for mortality and cardiovascular disease (CVD). This individualparticipant meta-analysis explored whether the relation of hypertension, death or CVD with 24-h urinary sodium excretion (UVNA) or sodium-to-potassium (UNAK) ratio was modified by birth weight. Methods: Families were randomly enrolled in the Flemish Study on Genes, Environment and Health Outcomes (19852004) and the European Project on Genes in Hypertension (1999- 2001). Categories of birth weight, UVNA and UNAK (2500-4000, >4000 g; 4.6 g; and 2, respectively) were coded using deviation-from-mean coding and analyzed by Kaplan- Meier survival functions and linear and Cox regression. Results: The study population was subdivided into the Outcome (n = 1945), Hypertension (n = 1460) and Blood Pressure cohorts (n 1/4 1039) to analyze the incidence of mortality and cardiovascular endpoints, hypertension and BP changes as function of UVNA changes. The prevalence of low/medium/high birth weight in the Outcome cohort was 5.8/84.5/9.7%. Over 16.7 years (median), rates were 4.9, 8 and 27.1% for mortality, CVD and hypertension, respectively, but were not associated with birth weight. Multivariable-adjusted hazard ratios were not significant for any endpoint in any of the birth weight, UVNA and UNAK strata. Adult body weight tracked with birth weight (P< 0.0001). The partial r in the low-birth-weight group associating changes from baseline to follow-up in UVNA and SBP was 0.68 (P = 0.023) but not significant in other birth weight groups. Conclusion: This study did not substantiate its prior hypothesis but showed tracking of adult with birth weight and suggest that low birth weight increases salt sensitivity

    Assessment of the one-year Efficacy and Safety of Tofacitinib in biologic-refractory patients with Ulcerative Colitis: a real-world Belgian cohort study

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    peer reviewedIntroduction: Tofacitinib, an oral Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. Efficacy and safety data from long-term real-world studies are scarce. Aim: The aim of the study was to evaluate the real-world long-term efficacy and safety of tofacitinib in a Belgian cohort of patients with refractory UC who were exposed to both anti-TNF and vedolizumab. Methods: We performed an observational, national, retrospective multicenter study including all patients whith active UC who started on tofacitinib between November 2018 and August 2019 in 26 Belgian centers (Ethics Committee approval number P2019/429, date: 10/12/2019; amendment for study extension received on 16/07/2020). Data were prospectively collected and retrospectively analyzed according to intention-to-treat. Clinical response (decrease from baseline in partial adapted Mayo score (stool frequency and rectal bleeding) by ‚Č• 1 and ‚Č• 30%), clinical remission (Partial Adapted Mayo score ‚ȧ 1), steroid-free clinical remission, endoscopic response (decrease from baseline in Mayo endoscopic subscore of ‚Č• 1), endoscopic remission (endoscopic Mayo subscore of 0), drug survival, need for colectomy and adverse events (AEs) were assessed at week 8, 16 and 52. Results: A total of 75 patients were included with a median follow-up of 45 weeks (IQR: 19-51). Patients were predominately men (59%), and median age at baseline was 44 years (IQR: 31-59). Median disease duration was 8 years (IQR: 4-17). Fifty-five percent had left-sided UC and 45% had pancolitis. Overall, 72 (96%), 51 (68%) and 6 (8%) patients were exposed to at least 1, 2 or 3 antiTNFs respectively, and 73 (97%) to vedolizumab. At baseline, 42 (56%) patients were under steroids. Median Partial Adapted Mayo score at baseline was 4 (IQR: 3-5), and median endoscopic Mayo subscore was 2 (IQR: 2-3). Thirty-nine (52%) patients required prolonged induction at 10mg twice daily for 8 additional weeks. Dose optimization was needed in 12 (16%) patients due to disease relapse after induction response, 9 (12%) of which could regain response. After 1 year, 52% and 43% of patients had experienced clinical response and clinical remission respectively, and 39% achieved steroid-free clinical remission. Endoscopic response and remission were observed in 37% and 9% of patients. Faecal calprotectin < 250 ¬Ķg/g at week 16 (OR: 0.03(95%CI: 0.003-0.4)) was a positive predictor of clinical remission at week 52. Overall, 34 (45%) patients discontinued tofacitinib (22 due to primary non response, 11 due to secondary loss of response and 1 due to AE) during follow-up with a median exposure duration of 17 weeks (IQR: 11-42). Among these patients, 6 underwent colectomy for disease worsening after a median treatment duration of 15 weeks (IQR: 11-19) and a median follow-up of 20 weeks (IQR: 12-25) , while the others switched to another medical therapy. Forty AEs were reported in 25 (33%) patients, with only one (pneumonia) leading to treatment discontinuation. The most common AEs were arthralgia and lower respiratory tract infections followed by herpes zoster, urinary tract and upper respiratory tract infections. Two cases of prostate cancer have been reported. No opportunistic infection, venous thromboembolism, pulmonary embolism or cardiovascular event were reported. A statistically significant increase of 43% in the low-density lipoprotein (LDL) level was observed between baseline and week 52 among patients in clinical remission at week 52 , with no significant changes in total cholesterol and high-density lipoprotein (HDL). Conclusions: Tofacitinib effectively induced long-term clinical and endoscopic response and remission in a refractory cohort of patients with UC in a real-world clinical setting. During this one-year follow-up, tofacitinib was relatively well tolerated with respect to adverse events

    Phenotyping patients with ischaemic heart disease at risk of developing heart failure: an analysis of the HOMAGE trial

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    Aims: We aim to characterize the clinical and proteomic profiles of patients at risk of developing heart failure (HF), with and without coronary artery disease (CAD) or prior myocardial infarction (MI). Methods and results: HOMAGE evaluated the effect of spironolactone on plasma and serum markers of fibrosis over 9 months of follow-up in participants with (or at risk of having) CAD, and raised natriuretic peptides. In this post hoc analysis, patients were classified as (i) neither CAD nor MI; (ii) CAD; or (iii) MI. Proteomic between-group differences were evaluated through logistic regression and narrowed using backward stepwise selection and bootstrapping. Among the 527 participants, 28% had neither CAD or MI, 31% had CAD, and 41% had prior MI. Compared with people with neither CAD nor MI, those with CAD had higher baseline plasma concentrations of matrix metalloproteinase-7 (MMP-7), galectin-4 (GAL4), plasminogen activator inhibitor 1 (PAI-1), and lower plasma peptidoglycan recognition protein 1 (PGLYRP1), whilst those with a history of MI had higher plasma MMP-7, neurotrophin-3 (NT3), pulmonary surfactant-associated protein D (PSPD), and lower plasma tumour necrosis factor-related activation-induced cytokine (TRANCE). Proteomic signatures were similar for patients with CAD or prior MI. Treatment with spironolactone was associated with an increase of MMP7, NT3, and PGLYRP1 at 9 months. Conclusions: In patients at risk of developing HF, those with CAD or MI had a different proteomic profile regarding inflammatory, immunological, and collagen catabolic processes
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