Comparison of different vascular risk engines in the identification of type 2 diabetes patients with high cardiovascular risk

Background: Some authors consider that secondary prevention should be conducted for all DM2 patients, while others suggest that the drug preventive treatment should start or be increased depending on each patient''s individual CVR, estimated using cardiovascular or coronary risk functions to identify the patients with a higher CVR. The principal objective of this study was to assess three different cardiovascular risk prediction models in type 2 diabetes patients. Methods: Multicentre, cross-sectional descriptive study of 3, 041 patients with type 2 diabetes and no history of cardiovascular disease. The demographic, clinical, analytical, and cardiovascular risk factor variables associated with type 2 diabetes were analysed. The risk function and probability that a cardiovascular disease could occur were estimated using three risk engines: REGICOR, UKPDS and ADVANCE. A patient was considered to have a high cardiovascular risk when REGICOR = 10 % or UKPDS = 15 % in 10 years or when ADVANCE = 8 % in 4 years. Results: The ADVANCE and UKPDS risk engines identified a higher number of diabetic patients with a high cardiovascular risk (24.2 % and 22.7 %, respectively) compared to the REGICOR risk engine (10.2 %). The correlation using the REGICOR risk engine was low compared to UKPDS and ADVANCE (r = 0.288 and r = 0.153, respectively//p < 0.0001). The agreement values in the allocation of a particular patient to the high risk group was low between the REGICOR engine and the UKPDS and ADVANCE engines (k = 0.205 and k = 0.123, respectively//p < 0.0001) and acceptable between the ADVANCE and UKPDS risk engines (k = 0.608). Conclusions: There are discrepancies between the general population and the type 2 diabetic patient-specific risk engines. The results of this study indicate the need for a prospective study which validates specific equations for diabetic patients in the Spanish population, as well as research on new models for cardiovascular risk prediction in these patients

Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

Background: Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM). Methods: Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy. Results: The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86-2.59), microvascular disease (OR 2.14; CI 95% 1.8-2.54) and insulin treatment (OR 1.82; CI 95% 1.39-2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80-0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21-0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91-0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09-1.3). Conclusions: One-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD

Comparison of different vascular risk engines in the identification of type 2 diabetes patients with high cardiovascular risk

Background: Some authors consider that secondary prevention should be conducted for all DM2 patients, while others suggest that the drug preventive treatment should start or be increased depending on each patient's individual CVR, estimated using cardiovascular or coronary risk functions to identify the patients with a higher CVR. The principal objective of this study was to assess three different cardiovascular risk prediction models in type 2 diabetes patients. Methods: Multicentre, cross-sectional descriptive study of 3,041 patients with type 2 diabetes and no history of cardiovascular disease. The demographic, clinical, analytical, and cardiovascular risk factor variables associated with type 2 diabetes were analysed. The risk function and probability that a cardiovascular disease could occur were estimated using three risk engines: REGICOR, UKPDS and ADVANCE. A patient was considered to have a high cardiovascular risk when REGICOR ≥ 10 % or UKPDS ≥ 15 % in 10 years or when ADVANCE ≥ 8 % in 4 years. Results: The ADVANCE and UKPDS risk engines identified a higher number of diabetic patients with a high cardiovascular risk (24.2 % and 22.7 %, respectively) compared to the REGICOR risk engine (10.2 %). The correlation using the REGICOR risk engine was low compared to UKPDS and ADVANCE (r = 0.288 and r = 0.153, respectively; p < 0.0001). The agreement values in the allocation of a particular patient to the high risk group was low between the REGICOR engine and the UKPDS and ADVANCE engines (k = 0.205 and k = 0.123, respectively; p < 0.0001) and acceptable between the ADVANCE and UKPDS risk engines (k = 0.608). Conclusions: There are discrepancies between the general population and the type 2 diabetic patient-specific risk engines. The results of this study indicate the need for a prospective study which validates specific equations for diabetic patients in the Spanish population, as well as research on new models for cardiovascular risk prediction in these patients. Keywords: Type 2 diabetes, Cardiovascular risk prediction, Cardiovascular disease, Risk prediction models, Primary predictio

Credibility assessment of patient-specific biomechanical models to investigate proximal junctional failure in clinical cases with adult spine deformity using ASME V&V40 standard

Computational models are increasingly used to assess spine biomechanics and support surgical planning. However, varying levels of model verification and validation, along with characterization of uncertainty effects limit the level of confidence in their predictive potential. The objective was to assess the credibility of an adult spine deformity instrumentation model for proximal junction failure (PJF) analysis using the ASME V&amp;V40:2018 framework. To assess model applicability, the surgery, erected posture, and flexion movement of actual clinical cases were simulated. The loads corresponding to PJF indicators for a group of asymptomatic patients and a group of PJF patients were compared. Model consistency was demonstrated by finding PJF indicators significantly higher for the simulated PJF vs. asymptomatic patients. A detailed sensitivity analysis and uncertainty quantification were performed to further establish the model credibility

Calpain translocation and activation as pharmacological targets during myocardial ischemia/reperfusion

Calpains contribute to reperfusion-induced myocardial cell death. However, it remains controversial whether its activation occurs during ischemia or reperfusion. We investigated the regulation and time-course of calpain activation secondary to transient ischemia and the efficacy of its inhibition at reperfusion as a therapeutic strategy to limit infarct size. In isolated rat hearts (Sprague-Dawley), ischemia induced a time-dependent translocation of m-calpain to the membrane that was not associated with calpain activation as assessed by proteolysis of its substrate α-fodrin. Translocation of calpain was dependent on Ca2+ entry through reverse mode Na+/Ca2+-exchange and was independent of acidosis. Calpain activation occurred during reperfusion, but only after intracellular pH (pHi) normalization, and was not prevented by inhibiting its translocation during ischemia with methyl-β-cyclodextrin. The intravenous infusion of MDL-28170 in an in vivo rat model with transient coronary occlusi

Studies on the role of apoptosis after transient myocardial ischemia: genetic deletion of the executioner caspases-3 and -7 does not limit infarct size and ventricular remodeling

Although it is widely accepted that apoptosis may contribute to cell death in myocardial infarction, experimental evidence suggests that adult cardiomyocytes repress the expression of the caspase-dependent apoptotic pathway. The aim of this study was to analyze the contribution of caspase-mediated apoptosis to myocardial ischemia-reperfusion injury. Cardiac-specific caspase-3 deficient/full caspase-7-deficient mice (Casp3/7DKO) and wild type control mice (WT) were subjected to in situ ischemia by left anterior coronary artery ligation for 45 min followed by 24 h or 28 days of reperfusion. Heart function was assessed using M-mode echocardiography. Deletion of caspases did not modify neither infarct size determined by triphenyltetrazolium staining after 24 h of reperfusion (40.0 ± 5.1 % in WT vs. 36.2 ± 3.6 % in Casp3/7DKO), nor the scar area measured by pricosirius red staining after 28 days of reperfusion (41.1 ± 5.4 % in WT vs. 44.6 ± 8.7 % in Casp3/7DKO). Morphometric and echocardiographic studies performed 28 days after the ischemic insult revealed left ventricular dilation and severe cardiac dysfunction without statistically significant differences between WT and Casp3/7DKO groups. These data demonstrate that the executioner caspases-3 and -7 do not significantly contribute to cardiomyocyte death induced by transient coronary occlusion and provide the first evidence obtained in an in vivo model that argues against a relevant role of apoptosis through the canonical caspase pathway in this context