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result(s) for
"Sposito, Andrei C."
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Cardiovascular effects of Glucagon-like peptide 1 (GLP-1) receptor agonists
2014
Patients with type 2 diabetes have a several-fold increased risk of developing cardiovascular disease when compared with nondiabetic controls. Myocardial infarction and stroke are responsible for 75% of all death in patients with diabetes, who present a 2-4× increased incidence of death from coronary artery disease. Patients with diabetes are considered for cardiovascular disease secondary prevention because their risk level is similar to that reported in patients without diabetes who have already suffered a myocardial infarction. More recently, with a better risk factors control, mainly in intensive LDL cholesterol targets with statins, a significant decrease in acute cardiovascular events was observed in population with diabetes. Together with other major risk factors, type 2 diabetes must be considered as an important cause of cardiovascular disease.
Glucagon like peptide-1 receptor agonists represent a novel class of anti-hyperglycemic agents that have a cardiac-friendly profile, preserve neuronal cells and inhibit neuronal degeneration, an anti-inflammatory effect in liver protecting it against steatosis, increase insulin sensitivity, promote weight loss, and increase satiety or anorexia.
This review is intended to rationally compile the multifactorial cardiovascular effects of glucagon-like peptide-1 receptor agonists available for the treatment of patients with type 2 diabetes.
Journal Article
GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data
by
Berwanger, Otávio
,
de Carvalho, Luiz Sérgio F.
,
Saraiva, José Francisco Kerr
in
Angina
,
Angina pectoris
,
Angiology
2018
Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. The strong connection between the severity of hyperglycaemia, metabolic changes secondary to T2DM and vascular damage increases the risk of macrovascular complications. There is a challenging demand for the development of drugs that control hyperglycaemia and influence other metabolic risk factors to improve cardiovascular outcomes such as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina and heart failure (major adverse cardiovascular events). In recent years, introduction of the new drug class of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has changed the treatment landscape as GLP-1RAs have become well-established therapies in T2DM. The benefits of GLP-1RAs are derived from their pleiotropic effects, which include appetite control, glucose-dependent secretion of insulin and inhibition of glucagon secretion. Importantly, their beneficial effects extend to the cardiovascular system. Large clinical trials have evaluated the cardiovascular effects of GLP-1RAs in patients with T2DM and elevated risk of cardiovascular disease and the results are very promising. However, important aspects still require elucidation, such as the specific mechanisms involved in the cardioprotective effects of these drugs. Careful interpretation is necessary because of the heterogeneity across the trials concerning the definition of cardiovascular risk or cardiovascular disease, baseline characteristics, routine care and event rates. The aim of this review is to describe the main clinical aspects of the GLP-1RAs, compare them using data from both the mechanistic and randomized controlled trials and discuss potential reasons for improved cardiovascular outcomes observed in these trials. This review may help clinicians to decide which treatment is most appropriate in reducing cardiovascular risk in patients with T2DM.
Journal Article
Effect of aluminum accumulation on bone and cardiovascular risk in the current era
by
Carbonara, Cinthia E. M.
,
França, Renata A.
,
Jorgetti, Vanda
in
Accumulation
,
Aluminum
,
Aluminum - analysis
2023
The prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era.
To detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation.
This is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered.
275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41-56) vs. 55 (43-61) years; p = 0.026], had lower body mass index [23.5 (21.6-25.5) vs. 24.3 (22.1-27.8) kg/m2; p = 0.017], higher dialysis vintage [108 (48-183) vs. 71 (28-132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0-3) vs. 0 (0-3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176-17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000-1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439-6.804; p = 0.004) and HR = 2.785 (CI: 1.120-6.928; p = 0.028].
An elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.
Journal Article
Impact of the COVID-19 pandemic on blood pressure control: a nationwide home blood pressure monitoring study
by
Mota-Gomes, Marco A.
,
Coca, Antonio
,
Feitosa, Audes D. M.
in
Blood Pressure
,
Blood Pressure Monitoring, Ambulatory
,
Brief Communication
2022
There are concerns that hypertension control may decrease during the COVID-19 pandemic. This study evaluated the impact of the COVID-19 pandemic on office blood pressure (OBP) and home blood pressure monitoring (HBPM) control in a large Brazilian nationwide sample. The results of an adjusted spline analysis evaluating the trajectory of OBP and HBPM control from 01/Jan/2019 to 31/Dec/2020 among independent participants who were untreated (n = 24,227) or treated (n = 27,699) with antihypertensive medications showed a modest and transient improvement in OBP control among treated individuals, which was restricted to the early months following the COVID-19 pandemic outbreak. Furthermore, slight reductions in OBP and HBPM values were detected in the early months following the COVID-19 pandemic outbreak among treated (n = 987) participants for whom blood pressure measurements before and during the pandemic were available, but not among untreated (n = 495) participants. In conclusion, we found no major adverse influence of the COVID-19 pandemic on OBP and HBPM control in a large nationwide sample.
Journal Article
The Reciprocal Relationship between LDL Metabolism and Type 2 Diabetes Mellitus
by
Hajduch, Eric
,
Le Goff, Wilfried
,
Bonilha, Isabella
in
Apolipoproteins
,
Atherosclerosis
,
Cardiomyopathy
2021
Type 2 diabetes mellitus and insulin resistance feature substantial modifications of the lipoprotein profile, including a higher proportion of smaller and denser low-density lipoprotein (LDL) particles. In addition, qualitative changes occur in the composition and structure of LDL, including changes in electrophoretic mobility, enrichment of LDL with triglycerides and ceramides, prolonged retention of modified LDL in plasma, increased uptake by macrophages, and the formation of foam cells. These modifications affect LDL functions and favor an increased risk of cardiovascular disease in diabetic individuals. In this review, we discuss the main findings regarding the structural and functional changes in LDL particles in diabetes pathophysiology and therapeutic strategies targeting LDL in patients with diabetes.
Journal Article
The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis
by
da Silva Ferreira, Isadora Maria Castilho
,
Sedenho-Prado, Luis Gustavo
,
Silva, Cleide Aparecida Moreira
in
Agonists
,
Analysis
,
Bias
2024
Background
Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus.
Methods
Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects.
Results
Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low.
Conclusions
Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable.
Trial registration
PROSPERO identifier: CRD42023393020.
Journal Article
CARDIAL-MS (CArdio-Renal-DIAbetes-Liver-Metabolic Syndrome): a new proposition for an integrated multisystem metabolic disease
by
de Araujo-Neto, João Marcello
,
Júnior, Wellington S. Silva
,
Sposito, Andrei C.
in
Adipocytes
,
Adipose tissue
,
Adiposopathy
2025
Background
Metabolic Syndrome—a constellation of insulin resistance, cardiovascular risk factors as hyperglycemia, hypertension, and dyslipidemia, and systemic metabolic dysfunction—may be driven by dysregulation of adipose tissue, which manifests as adiposopathy (pathogenic adipose tissue expansion or maldistribution), ectopic fat deposition (in the liver, muscle, pancreas, and cardiorenal systems), and altered secretion of adipokines/hepatokines. Weight gain, obesity, and/or unfavorable fat distribution create a scenario wherein the type, size, location, secretions, or even scarcity of adipocytes drive pathophysiological mechanisms leading to hepatic steatosis and steatohepatitis, type 2 diabetes, and heart and kidney disease. While recent frameworks, such as cardiovascular-kidney-metabolic syndrome, emphasize holistic staging, the central role of metabolic dysfunction-associated steatotic liver disease (MASLD) in multisystem morbidity remains underrecognized.
Main text
This narrative review synthesizes evidence linking MASLD and diabetes to cardiovascular and kidney diseases through shared pathways of adiposopathy, ectopic lipid accumulation, and dysregulated adipokine/hepatokine signaling. We propose CARDIAL-MS (CArdio-Renal-DIAbetes-Liver-Metabolic Syndrome), an expanded pathophysiological model that unifies these interactions into four progressive stages: (1) weight gain and dysfunctional adipose tissue; (2) metabolic risk factors and markers of risk; (3) cardiometabolic diseases and chronic kidney disease; and (4) advanced cardio-renal-liver-metabolic disease. By integrating MASLD as a pivotal component, CARDIAL-MS reframes metabolic syndrome as a continuum of interconnected organ injuries rather than isolated risk factors.
Conclusion
CARDIAL-MS provides a staging model to identify patients at critical transition points—from reversible metabolic disturbances to irreversible organ damage. This model emphasizes early interventions targeting adipose tissue health and ectopic fat deposition to mitigate the progression of metabolic cardiorenal diseases. By recognizing the syndromic nature of these conditions, CARDIAL-MS offers clinicians an actionable paradigm for risk stratification, timely diagnosis, and personalized prevention strategies.
Journal Article
Optimal timing for post-dialysis blood pressure measurement: relationship with home blood pressure monitoring
2025
In hemodialysis patients, blood pressure (BP) measured at the postdialysis period (POSBP) can be used to diagnose hypertension. However, the optimal time point for POSBP remains uncertain. This cross-sectional study evaluated 210 long-term dialysis patients (66.7% men; age = 56.9 ± 15.7 years), who underwent POSBP measurements at three time points [immediately after dialysis period ended (POSBP1); after blood return (POSBP2) and after fistula hemostasis or catheter sealing (POSBP3)] and home BP monitoring (HBPM) over one week. POSBP1, POSBP2, POSBP3 and HBPM values were 139.1 ± 22.4/73.2 ± 12.5, 142.8 ± 22.8/74.3 ± 12.3, 142.8 ± 21.8/74.0 ± 12.2 and 131.2 ± 21.2/77.9 ± 12.1 mmHg, respectively. Systolic POSBP3 and POSBP2 were significantly greater (
p
< 0.05) than systolic POSBP1. POSBP3 had the greatest correlation with HBPM, while elevated (>130/80 mmHg) POSBP3 showed the highest numerical accuracy (AUC [95% CI] = 0.696 [0.638–0.754]) and concordance (kappa coefficient = 0.41) with elevated HBPM (≥130/80 mmHg) compared with POSBP1 and POSBP2. These findings suggest that POSBP3 may be a preferable measurement for assessment of POSBP in hemodialysis patients.
Journal Article
Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy
by
Coelho, Otávio Rizzi
,
Drobni, Zsofia D.
,
Matos-Souza, José Roberto
in
692/4019/592/1540
,
692/4028/67/1347
,
692/53/2423
2021
There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m
2
) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310–517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (
P
< 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m
2
and 8.13 ± 2 g/m
2
, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (
P
< 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = −0.46;
P
< 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.
Journal Article
Prevalence of masked and white-coat hypertension among individuals with diabetes: insights from web-based home blood pressure monitoring in the Brazilian population
2024
The association between diabetes mellitus (DM) and masked hypertension (MH) in ambulatory blood pressure (BP) monitoring is established, but its relationship with home BP monitoring (HBPM) remains uncertain. This web-based database study compared BP phenotypes in individuals using (n = 51,194; 6.05% with DM) and not using (
n
= 55,320; 0.63% with DM) antihypertensive medications (AH) undergoing HBPM. Multivariable logistic regression analysis revealed similar MH and white-coat hypertension (WCH) prevalence in individuals with or without DM, irrespective of AH use. However, among AH non-users, DM was associated with a higher likelihood of normotension (OR 1.35, 95%CI 1.09–1.66;
p
= 0.006) and a lower likelihood of sustained hypertension (OR 0.77, 95%CI 0.60–0.99;
p
= 0.039) compared to individuals without DM. These findings suggest that while DM does not significantly impact MH and WCH in HBPM, it may influence normotension and sustained hypertension rates in AH non-users.
Likelihood of diabetes mellitus according to blood pressure phenotypes. AH – antihypertensive medications; CH – controlled hypertension; MH – masked hypertension; MUCH – masked uncontrolled hypertension; NT – normotension; SH – sustained hypertension; SUCH – sustained uncontrolled hypertension; WCH – white-coat hypertension; WUCH – white-coat uncontrolled hypertension.
Journal Article