ATTRIBUTABLE RISK ESTIMATE OF SEVERE PSORIASIS ON MAJOR CARDIOVASCULAR EVENTS

Le principal défi du CTA est de faire face à la rapide mutation du milieu dans lequel nous travaillons : nous adapter à l’évolution fulgurante des technologies de l’information et de la communication (TIC) et, en réponse à certains des paradigmes du développement qui ont mal vieilli, identifier de nouveaux modèles et des mécanismes novateurs répondant aux besoins actuels de développement. En 2006, nous nous sommes démarqués de l’approche “business as usual”. Nous avons introduit quelques changements dans notre gestion et notre culture organisationnelle et, par là même, dans notre état d’esprit. Dr. Hansjörg Neun Directeur, CTALe principal défi du CTA est de faire face à la rapide mutation du milieu dans lequel nous travaillons : nous adapter à l’évolution fulgurante des technologies de l’information et de la communication (TIC)... Dr. Hansjörg NeunDirecteur, CT

Proteomic Alterations of HDL in Youth with Type 1 Diabetes and their Associations with Glycemic Control: A Case-Control Study

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. Results: Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P \u3c 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P \u3c 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. Conclusions: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT0227509

Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study

Aims Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown. Methods and Results We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels (P \u3c 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P \u3c 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P \u3c 0.001), death (1.20; 1.09,1.33, P \u3c 0.001), and combined MI/death (1.23; 1.13–1.34, P \u3c 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio. Conclusions In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials

Effect of Metformin on the High-Density Lipoprotein Proteome in Youth with Type 1 Diabetes

Background: Youth with type 1 diabetes (T1D) have normal or elevated High-Density Lipoprotein Cholesterol (HDL-C), however, the function of HDL, partly mediated by the HDL proteome, may be impaired. Metformin can be used as an adjunct therapy in youth with T1D, but its effects on the HDL proteome are unknown. Objective: To determine the effect of metformin on the HDL proteome. Subjects: Youth (12-20 years old) with T1D who had a BMI \u3e 90th percentile, HbA1c \u3e 8.0% and Tanner stage 5. Methods: Double-blinded, placebo-controlled randomized sub-study. We examined the effects of metformin (n = 25) or placebo (n = 10) after 6 months on HDL proteome. Changes in HDL proteins were measured by data-independent acquisition (DIA) mass spectrometry and compared between treatment groups. As a secondary outcome, associations between proteins of interest and the most studied function of HDL, the cholesterol efflux capacity (CEC), was examined. Results: The relative abundance of 84 HDL-associated proteins were measured. Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha-2-macroglobulin (A2MG; +29.8%, p = .049). Metformin did not significantly affect CEC. Changes in affected HDL proteins did not correlate with CEC. Conclusions: Despite having little effect on HDL-C, metformin increased PGRP2 and A2MG protein on HDL in youth with T1D, but had no significant effect on CEC. Further studies are needed to understand the impact of PGRP2 and A2MG on other HDL functions

Effect of psoriasis severity on hypertension control: a population-based study in the United Kingdom.

IMPORTANCE: Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown. OBJECTIVE: To determine the association between uncontrolled blood pressure and psoriasis, both overall and according to objectively measured psoriasis severity, among patients with diagnosed hypertension. DESIGN, SETTING, AND PARTICIPANTS: Population-based cross-sectional study nested in a prospective cohort drawn from The Health Improvement Network (THIN), an electronic medical records database broadly representative of the general population in the United Kingdom. The study population included a random sample of patients with psoriasis (n = 1322) between the ages of 25 and 64 years in THIN who were included in the Incident Health Outcomes and Psoriasis Events prospective cohort and their age- and practice-matched controls without psoriasis (n = 11,977). All included patients had a diagnosis of hypertension; their psoriasis diagnosis was confirmed and disease severity was classified by their general practitioners. MAIN OUTCOMES AND MEASURES: Uncontrolled hypertension was defined as a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher based on the blood pressure recorded closest in time to the assessment of psoriasis severity. RESULTS: There was a significant positive dose-response relationship between uncontrolled hypertension and psoriasis severity as objectively determined by the affected body surface area in both unadjusted and adjusted analyses that controlled for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (adjusted odds ratio [aOR], 0.97; 95% CI, 0.82-1.14 for mild psoriasis; aOR, 1.20; 95% CI, 0.99-1.45 for moderate psoriasis; and aOR, 1.48; 95% CI, 1.08-2.04 for severe psoriasis; P = .01 for trend). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, although not statistically significantly so (aOR, 1.10; 95% CI, 0.98-1.24). CONCLUSIONS AND RELEVANCE: Among patients with hypertension, psoriasis was associated with a greater likelihood of uncontrolled hypertension in a dose-dependent manner, with the greatest likelihood observed among those with moderate to severe psoriasis defined by 3% or more of the body surface area affected. Our data suggest a need for more effective blood pressure management, particularly among patients with more severe psoriasis

Dysglycemia but not lipids is associated with abnormal urinary albumin excretion in diabetic kidney disease: a report from the Kidney Early Evaluation Program (KEEP)

BACKGROUND: The relationship between glycemic control and lipid abnormalities with urinary albumin-creatinine ratio (ACR) in chronic kidney disease (CKD) patients with diabetes mellitus (DM) is unknown. We sought to investigate the association of dyslipidemia and glycemic control with levels of albuminuria in the National Kidney Foundation (NKF) Kidney Early Evaluation Program (KEEP) participants with DM and CKD stage 3 or higher. METHODS: We performed a cross-sectional study of 6639 eligible KEEP patients with DM and CKD Stage 3 to 5 from June 2008 to December 2009. Multivariate logistic regression was used to evaluate the association of lipid parameters (per 10 mg/dl change in serum level) and glycosylated hemoglobin (HbA1c) values with three degrees of albuminuria normo (<30 mg⁄g), micro (30 to 300 mg⁄g) and macro (>300 mg⁄g). RESULTS: 2141 KEEP participants were included. HbA1c levels were strongly associated with micro-albuminuria (compared to normo-albuminuria) and macro-albuminuria (compared to normo-albuminuria and micro-albuminuria). Each 1.0% increase in HbA1c increased the odds of micro-albuminuria by 32% (OR 1.32, 95% CI 1.23-1.42) and the odds of macro-albuminuria (vs. microalbuminuria) by 16% (OR 1.16, 95% CI 1.05-1.28). Only increases in serum HDL were associated with decreased odds of micro-albuminuria; otherwise, the association between other components of the serum lipid profile with urinary ACR did not reach statistical significance. CONCLUSION: In this cross-sectional study of 2141 KEEP participants with DM and CKD stages 3–5, overall glycemic control but not lipids were associated with abnormal urinary albumin excretion, a marker of increased risk for progressive disease

Effect of Niacin Monotherapy on High Density Lipoprotein Composition and Function

BACKGROUND: Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL\u27s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function. METHODS: A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement. RESULTS: In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q \u3c 0.01; LDL-C - 20%, q \u3c 0.01; and triglyceride - 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q \u3c 0.05). Niacin did not impact HDL\u27s ability to influence endothelial function. CONCLUSION: Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction

Oxidized low-density lipoprotein associates with cardiovascular disease by a vicious cycle of atherosclerosis and inflammation: A systematic review and meta-analysis

BackgroundLow-density lipoprotein cholesterol (LDL-C) is an established marker for cardiovascular disease (CVD) and a therapeutic target. Oxidized LDL (oxLDL) is known to be associated with excessive inflammation and abnormal lipoprotein metabolism. Chronic inflammatory diseases confer an elevated risk of premature atherosclerosis and adverse cardiovascular events. Whether oxLDL may serve as a potential biomarker for CVD stratification in populations with chronic inflammatory conditions remains understudied.ObjectiveTo perform a systematic review and meta-analysis evaluating the relationship between oxLDL and CVD (defined by incident CVD events, carotid intima-media thickness, presence of coronary plaque) in patients with chronic inflammatory diseases.MethodsA systematic literature search was performed using studies published between 2000 and 2022 from PubMed, Cochrane Library, Embase (Elsevier), CINHAL (EBSCOhost), Scopus (Elsevier), and Web of Science: Core Collection (Clarivate Analytics) databases on the relationship between oxLDL and cardiovascular risk on inflamed population. The pooled effect size was combined using the random effect model and publication bias was assessed if P &lt; 0.05 for the Egger or Begg test along with the funnel plot test.ResultsA total of three observational studies with 1,060 participants were ultimately included in the final meta-analysis. The results demonstrated that oxLDL is significantly increased in participants with CVD in the setting of chronic inflammatory conditions. This meta-analysis suggests that oxLDL may be a useful biomarker in risk stratifying cardiovascular disease in chronically inflamed patients