Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis

Testuz, Ariane; Nguyen, Virginia; Mathieu, Tiffany; Arangalage, Dimitri; Kubota, Naozumi; Codogno, Isabelle; Tubiana, Sarah; Estellat, Candice; Cimadevilla, Claire; Vahanian, Alec; Messika–Zeitoun, David

doi:10.1016/j.ijcard.2017.06.104

Cited by 25 publications

(20 citation statements)

References 24 publications

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“…However, the authors evaluated only levels of fasting glucose, reflecting short-term glucose dynamics. Neither the levels of HbA1c, fructosamine nor AGEs in their cohort were assessed [27], while our study showed that in AS patients with well-controlled type 2 DM an influence of hyperglycemia on AS severity is minor.…”

Section: Table 3 Multivariate Associations Between Echocardiographic contrasting

confidence: 67%

“…CI confidence interval; for other abbreviations see Tables 1 and 2 Variable AVA, estimate (95% CI) [26]. On the contrary, Testuz et al [27] failed to demonstrate an association between AS progression and metabolic syndrome or diabetes during 3-years follow-up. However, the authors evaluated only levels of fasting glucose, reflecting short-term glucose dynamics.…”

Section: Table 3 Multivariate Associations Between Echocardiographic mentioning

confidence: 97%

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Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

Kopytek

Ząbczyk

Mazur

et al. 2020

Cardiovasc Diabetol

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Background: Accumulation of advanced glycation end products (AGEs) leads to chronic glycation of proteins and tissue damage, particularly in patients with diabetes mellitus (DM). We aimed to evaluate whether increased accumulation of AGEs in patients with aortic stenosis (AS) and concomitant type 2 diabetes (DM) is associated with AS severity. Methods: We prospectively enrolled 76 patients with severe AS (47.1% males; nonDM), aged 68 [66-72] years, and 50 age-matched DM patients with a median blood glucose level of 7.5 [5.9-9.1] mM and glycated hemoglobin (HbA1c) of 6.8 [6.3-7.8]%, scheduled for aortic valve replacement. Valvular expression of AGEs, AGEs receptor (RAGE), interleukin-6 (IL-6), and reactive oxygen species (ROS) induction were evaluated ex vivo by immunostaining and calculated as the extent of positive immunoreactive areas/total sample area. Plasma levels of AGEs and soluble RAGE (sRAGE) were assessed by ELISAs. Results: Subjects with DM had increased valvular expression of both AGEs (6.6-fold higher, 15.53 [9.96-23.28]%) and RAGE (1.8-fold higher, 6.8 [4.9-8.45]%) compared to nonDM patients (2.05 [1.21-2.58]% and 2.4 [1.56-3.02]%, respectively; both p < 0.001). Plasma levels of AGEs (12-fold higher) and sRAGE (1.3-fold higher) were elevated in DM patients, compared to nonDM (both p < 0.0001). The percentage of valvular ROS-positive (2.28 [1.6-3.09] vs. 1.15 [0.94-1.4]%, p < 0.0001) but not IL-6-positive areas was higher within DM, compared to nonDM valves. In DM patients, the percentage of valvular AGEs-and RAGE-positive areas correlated with HbA1c (r = 0.77, p < 0.0001 and r = 0.30, p = 0.034). Similarly, plasma AGEs and sRAGE levels were associated with HbA1c in the DM group (r = 0.32, p = 0.024 and r = 0.33, p = 0.014, respectively). In all DM patients, we found an association between the amount of valvular AGEs and the disease severity measured as aortic valve area (AVA; r = 0.68, p < 0.0001). Additionally, in DM patients with HbA1c > 7% (n = 24, 48%) we found that valvular expression of AGEs correlated with mean transvalvular pressure gradient (PG mean ; r = 0.45, p = 0.027). Plasma AGEs levels in the whole DM group correlated with AVA (r = − 0.32, p = 0.02), PG mean (r = 0.31, p = 0.023), and PG max (r = 0.30, p = 0.03). Conclusions: Our study suggests that poorly-controlled diabetes leads to increased AGEs and RAGE valvular accumulation, which at least partially, might result in AS progression in DM patients.

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Section: Table 3 Multivariate Associations Between Echocardiographic contrasting

confidence: 67%

Section: Table 3 Multivariate Associations Between Echocardiographic mentioning

confidence: 97%

Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

Kopytek

Ząbczyk

Mazur

et al. 2020

Cardiovasc Diabetol

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“…Heart valve homeostasis is tightly controlled by valve interstitial cells (VICs) embedded in ECM, valve endothelial cells (VECs) covering the leaflet, and circulant and resident immune cells. When CAVD develops, lipid deposition, inflammation and angiogenesis occur while VICs are entering an osteogenic program as a response to exposure to risk factors including age, congenital heart defect, male gender, tobacco use, diabetes, hypertension, obesity and dyslipidemia ( 7 – 9 ). As a result, homeostasis is disrupted, ECM is remodeled, and formation of calcium nodules occurs.…”

Section: Introductionmentioning

confidence: 99%

Advances in Pathophysiology of Calcific Aortic Valve Disease Propose Novel Molecular Therapeutic Targets

Hulin

Hego

Lancellotti

et al. 2018

Front. Cardiovasc. Med.

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Calcific Aortic Valve Disease (CAVD) is the most common heart valve disease and its incidence is expected to rise with aging population. No medical treatment so far has shown slowing progression of CAVD progression. Surgery remains to this day the only way to treat it. Effective drug therapy can only be achieved through a better insight into the pathogenic mechanisms underlying CAVD. The cellular and molecular events leading to leaflets calcification are complex. Upon endothelium cell damage, oxidized LDLs trigger a proinflammatory response disrupting healthy cross-talk between valve endothelial and interstitial cells. Therefore, valve interstitial cells transform into osteoblasts and mineralize the leaflets. Studies have investigated signaling pathways driving and connecting lipid metabolism, inflammation and osteogenesis. This review draws a summary of the recent advances and discusses their exploitation as promising therapeutic targets to treat CAVD and reduce valve replacement.

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“…The association between T2DM and AS is due to the increased development of atherosclerosis in diabetic patients [ 5 ]. The activation of the rennin-angiotensin-aldosterone axis, elevation of inflammatory interleukins, production of free radicals, and glycosylation of proteins lead to an increase in profibrotic and calcific processes causing aortic valvular calcification and progression to AS [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Transcatheter aortic valve implantation and surgical aortic valve replacement among hospitalized patients with and without type 2 diabetes mellitus in Spain (2014–2015)

Méndez‐Bailón

Lorenzo-Villalba²,

Muñoz‐Rivas

et al. 2017

Cardiovasc Diabetol

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BackgroundType 2 diabetes mellitus (T2DM) is strongly related to the in-hospital and short-term prognosis in patients with cardiovascular diseases needing surgical or invasive interventions. How T2DM might influence the treatment of aortic stenosis (AS) has not been completely elucidated for surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). The aims of this study were: (1) to describe the use of aortic valve replacement procedures (TAVI and SAVR) among hospitalized patients with and without T2DM; and (2) to identify factors associated with in hospital mortality (IHM) among patients undergoing these procedures.MethodsWe analyzed data from the Spanish National Hospital Discharge Database between January 1, 2014 and December 31, 2015 for patients aged ≥ 40 years. We selected patients whose medical procedures included TAVI (ICD-9-CM codes 35.05, 35.06) and SAVR (ICD-9-CM codes 35.21, 35.22). We stratified each cohort by diabetes status: T2DM (ICD-9-CM codes 250.x0, 250.x2) and no diabetes. We retrieved data about specific comorbidities, risk factors, procedures, and specific in-hospital postoperative complications. Hospital outcome variables included IHM, and length of hospital stay (LOHS).ResultsWe identified a total of 2141 and 16,013 patients who underwent TAVI (n = 715; 33.39% with T2DM) and SAVR (n = 4057; 25.33% with T2DM). In patients who underwent TAVI we found no differences in IHM (3.64% in T2DM vs. 5.12% in non-T2DM, p = 0.603). In the cohort of SAVR, mean LOHS was significantly lower in patients with T2DM than in non-diabetic patients (13.77 vs. 17.27 days). IHM was lower in patients with T2DM (4.36% vs. 6.31%, p < 0.01). After multivariable adjustment for both procedures, patients with T2DM had significantly lower IHM than patients without diabetes (adjusted OR 0.60; IC 95% 0.37–0.99 for TAVI and adjusted OR 0.80; IC 95% 0.66-0-96 for SAVR).ConclusionsT2DM diabetic patients with AS undergoing a valvular replacement procedure through SAVR or TAVI did not have a worse prognosis compared to non-diabetic patients during hospitalization, showing lower IHM after multivariable adjustment. However, given the limitations of administrative data more prospective studies and clinical trials aimed at evaluating the influence of these procedures in diabetic patients with AS are needed.Electronic supplementary materialThe online version of this article (10.1186/s12933-017-0631-6) contains supplementary material, which is available to authorized users.

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Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis

Cited by 25 publications

References 24 publications

Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

Advances in Pathophysiology of Calcific Aortic Valve Disease Propose Novel Molecular Therapeutic Targets

Transcatheter aortic valve implantation and surgical aortic valve replacement among hospitalized patients with and without type 2 diabetes mellitus in Spain (2014–2015)

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