Abstract 14866: Plasma B-type Natriuretic Peptide Levels Are Associated With Future Cardiovascular Events in Patients With Type 2 Diabetes Mellitus Without Known Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shota Ikeda ◽  
Keisuke Shinohara ◽  
Nobuyuki Enzan ◽  
Shouji Matsushima ◽  
Takeshi Tohyama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Natriuretic Peptide ◽  
Vascular Events ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Cv Disease

Introduction: B-type natriuretic peptide (BNP) is known to predict future cardiovascular (CV) events in patients with known CV disease. However, these associations have not been investigated in patients with type 2 diabetes mellitus (T2DM) without known CV disease. We investigated whether BNP levels are associated with CV events among T2DM patients without known CV disease using the dataset of EMPATHY study. Methods and Results: The EMPATHY was a randomized controlled trial of intensive statin therapy in T2DM patients without known CV disease. CV events were defined as composite of cardiac (acute coronary syndrome and coronary revascularization [excluding heart failure]), cerebral, and vascular events. A total of 4704 patients without CV events or death during the first 12 months were included and 114 CV events occurred during a median follow-up of 37.8 months. The patients were divided based on quartile of baseline BNP levels (Q1: <7.4, Q2: 7.4-14.8, Q3: 14.8-28.7, Q4: ≥28.7 [pg/mL]). Compared to the lowest quartile of BNP, only the highest quartile was associated with increased risk for CV events after adjustment (HR 2.96, 95% CI 1.29-6.79, p=0.010). Using this highest quartile cutoff, we categorized BNP <28.7 pg/mL as low BNP and BNP ≥28.7 pg/mL as high BNP. Compared to patients with low BNP, the adjusted HRs for CV events were 2.12 (95% CI 1.35-3.34, p=0.001) in patients with high BNP at baseline and 2.64 (95% CI 1.67-4.17, p<0.001) in those with high BNP at 12 months. In analysis using serial measurement, patients who had repeatedly high BNP or had low BNP at baseline and high BNP at 12 months were in significantly higher risk for CV events compared to those who had repeatedly low BNP (HR 3.28, 95% CI 1.90-5.66, p<0.001 or HR 2.65, 95% CI 1.44-4.87, p=0.002, respectively), whereas those who had high BNP at baseline and low BNP at 12 months were not (HR 1.99, 95% CI 0.90-4.39, p=0.089). Conclusion: Increased BNP levels were associated with higher risk of CV events (excluding heart failure) in T2DM patients without known CV disease. HR for CV events was greater in patients with repeatedly high BNP than in those with high BNP at only one of the two measurements, suggesting that serial BNP measurement may be more useful for predicting future CV events in T2DM patients.

Abstract 16139: A Targeted Proteomic Approach to Identify Circulating Biomarkers of Heart Failure Risk in Patients With Type 2 Diabetes Mellitus in DECLARE-TIMI 58

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
David Berg ◽  
Stephen D Wiviott ◽  
Itamar RAZ ◽  
Frederick Kamanu ◽  
KyungAh Im ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Natriuretic Peptide ◽  
Proteomic Approach ◽  
Increased Risk ◽  
Fgf 23

Background: Patients (pts) with type 2 diabetes mellitus (T2DM) are at increased risk of heart failure (HF); however, the underlying mechanisms by which T2DM contributes to HF are incompletely understood. Hypothesis: We aimed to identify biological pathways associated with risk of hospitalization for HF (HHF) in a well-characterized cohort with T2DM followed for a median of 4.2 yrs. Methods: DECLARE-TIMI 58 was a randomized trial of dapagliflozin in pts with T2DM. We performed a nested case-control study of 184 candidate biomarkers (Olink CV II and CV III) in pts hospitalized for HF (n=432) and controls matched on age, sex, prior HF, prior CV disease, and f/u time (n=432). We evaluated associations between baseline biomarkers and HHF using logistic regression with a stringent threshold for significance (Bonferroni). Biomarkers were ranked according to Wald χ 2 values. ORs for the top 10 biomarkers were further adjusted for the components of the TIMI Risk Score for HF in Diabetes (AF, UACR, eGFR, CAD). ORs are per 1-SD. Results: 45 biomarkers were significantly associated with HHF. The 10 strongest associations were seen with N-terminal pro-B type natriuretic peptide (NT-proBNP), B type natriuretic peptide (BNP), spondin-1 (SPON1), insulin-like growth factor-binding protein 7 (IGFBP7), interleukin-6 (IL-6), fibroblast growth factor-23 (FGF-23), transferrin receptor protein 1 (TR), metalloproteinase inhibitor 4 (TIMP4), matrix metalloproteinase-2 (MMP-2), C-X-C motif chemokine 16 (CXCL16) ( Fig ). All 10 biomarkers were significantly associated with HHF both in pts with and without a history of HF. These proteins represent pathobiological axes implicated in hemodynamic stress, inflammation, myocardial hypertrophy, and cellular senescence, among others. Conclusions: A targeted proteomic approach identified established (NT-proBNP, BNP), investigational (IGFBP7, FGF-23, IL-6, TR, TIMP4, MMP-2, CXCL16), and novel (SPON1) biomarkers of HHF in pts with T2DM.

scholarly journals Association between Markers of Fibrosis and Heart Failure Incidence in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Denis A. Lebedev ◽  
Elena A. Lyasnikova ◽  
Elena Yu. Vasilyeva ◽  
Nikolai P. Likhonosov ◽  
Maria Yu. Sitnikova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Type I ◽  
Procollagen Type ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and chronic heart failure (HF) have close association, and several biomarkers have been studied to better understand this association and improve prediction of HF in T2DM. Furthermore, in recent clinical trials, sodium glucose cotransporter 2 inhibitors (SGLT2i), glucose-lowering drugs, improved HF outcomes. The objective of the present study was to evaluate association between circulating biomarkers of fibrosis and incidence of HF with preserved ejection fraction (HFpEF) in patients with T2DM receiving sodium glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods. At baseline, transthoracic echocardiography and laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), soluble suppression of tumorigenesis-2 (sST2), galectin-3 (Gal-3), C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1) were done. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by a cardiologist) was obtained. Results. Seventy-two patients were included in the study. The mean age was 57 (49.7; 63.2) years; 44% were female. Most patients had T2DM for more than 4 years. All patients were overweight or had obesity, and 93% patients had arterial hypertension (AH). After 3 years of follow-up, HFpEF was established in 21% patients. Patients were divided into two groups according to the presence of HFpEF, and baseline characteristics were compared. Patients with HF were older and had longer diabetes and AH duration and higher Nt-proBNP, Gal-3, PIIINP, and PICP levels at baseline than patients without HF (all p < 0.05 ). Gal − 3 > 10  ng/ml ( OR = 2.25 ; 95% CI, 1.88–5.66; p = 0.01 ) and NT − pro − BNP > 80  pg/ml ( OR = 2.64 ; 95% CI, 1.56–4.44; p = 0.001 ) were associated with increased risk of HF incidence. Age > 60 years, diabetes duration > 10 years, and presence of abdominal obesity were independent predictors of HFpEF as well. Conclusions. T2DM patients treated with SLGT2i, who developed HFpEF after 3 years of follow-up, had higher PICP, PIIINP, Gal-3, and NT-proBNP serum concentrations at baseline, and Gal-3 level was an independent predictor of HFpEF.

scholarly journals Empagliflozin as a new management strategy on outcomes in patients with type 2 diabetes mellitus

2016 ◽  
Vol 19 (6) ◽  
pp. 494-510 ◽  
Author(s):  
Vladimir V. Salukhov ◽  
Tatiana Y. Demidova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mechanism Of Action ◽  
Glucose Lowering ◽  
Long Duration ◽  
Increased Risk ◽  
Urinary Glucose ◽  
Cv Disease

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular (CV) complications. Although hyperglycaemia contributes to the pathogenesis of atherosclerosis and heart failure in these patients, glucose-lowering strategies did not have a significant effect on reducing CV risk, particularly in patients with a long duration of type 2 diabetes mellitus and prevalent CV disease (CVD). Sodium-glucose linked transporter-2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic medications that increase glycaemic control via insulin-dependent mechanism of action associated with increased urinary glucose excretion.In this review, we present an analysis of the Empa-Reg Outcomes investigation, focussed on assessing the CV safety of empagliflozin, an inhibitor of SGLT2. We discuss the impressive results of trials that provide evidence on the cardiac and renal properties of empagliflozin. We present and analyse the current hypothesis on the mechanism of action of glucose-lowering medication, which has such a severe and complex impact on outcomes in patients with type 2 diabetes at high CV risk.

scholarly journals Heart failure in diabetes: From an increased risk to a treatment target

2018 ◽  
Vol 21 (5) ◽  
pp. 399-403 ◽  
Author(s):  
Eberhard Standl
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Risk ◽  
Glycaemic Control ◽  
Treatment Target ◽  
Poor Glycaemic Control ◽  
Increased Risk

Heart failure (HF) is one of the most common comorbidities of type 2 diabetes mellitus (T2DM) and poor glycaemic control can worsen the HF outcomes and increase the risk of hospitalisations. With the entry of several antihyperglycaemic agents for the management of T2DM over the last decade, there has been an increasing concern regarding the cardiovascular (CV) safety profile of these agents. In view of this, FDA mandated the demonstration of cardiovascular risk-benefit profile of these agents through specifically designed CV outcome trials. Although we have several findings from these trials, none of them included HF as a primary endpoint indicating the need of trials focusing on HF. Here, we briefly discuss the results of the CV outcome trials in the context of HF.

scholarly journals NT-pro brain natriuretic peptide in patients with type 2 diabetes mellitus without overt heart failure: a hospital based cross sectional study

2021 ◽  
Vol 8 (4) ◽  
pp. 563
Author(s):  
Sanjay Varma ◽  
Archana Toppo ◽  
Khagdev Ram ◽  
Rajeev Lochan Khare ◽  
Yogendra Malhotra ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Brain Natriuretic Peptide ◽  
Diastolic Dysfunction ◽  
Natriuretic Peptide ◽  
Age Group ◽  
Cross Sectional

Background: Increased secretion of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) occurs mainly with increased tension in the ventricular walls, decreased oxygen supply, acute myocardial infarction, chronic cardiac heart failure, and in hypertrophy of the heart. Objective was to find out the prevalence and profile of NT-pro BNP levels in patients with type 2 diabetes mellitus (DM) without overt heart failure.Methods: Hospital based cross sectional observational study was conducted in the Department of Medicine, Pt. JNM Medical College and associated Dr. BRAM Hospital Raipur, Chhattisgarh involving 106 patients of type 2 DM during the period of April 2019 to April 2020, after ethical approval from institutional ethical committee.Results: The levels of NT pro BNP was found to be elevated in 87.7% patients of DM type 2. Majority of them were from 51-60 years age group (35.5%). Elevated NT proBNP levels was seen in 23.58% of patients having grade I diastolic dysfunction, 3.7% patients with grade II diastolic dysfunction and 1.88% patients having grade III diastolic dysfunction on echocardiography out of the 106 patients. Regardless of presence of diastolic dysfunction on echo, 93 (87.73%) patients out of the total study group of 106 patients had elevated BNP suggesting cardiac dysfunction. In the present study, 30.19% patients with diabetes were found to have varying degrees of diastolic dysfunction on echocardiography.Conclusions: The prevalence of elevated NT pro BNP was 87.7%. Commonly observed age group with elevated NT pro BNP was 51-60 years. NT pro BNP was elevated in 88.7% of males and in 88.36% of females. Prevalence of elevated NT pro BNP was higher in grade 1 diastolic dysfunction with DM duration of more than 5 years (33.3%). Higher prevalence of elevated NT pro BNP was seen in grade I diastolic dysfunction (23.58%). 

Abstract 13289: Incidence of Heart Failure Hospital Admissions Among Type 2 Diabetes Mellitus Patients and the Potential Impact of SGLT2 Inhibitors in Japan: A Population-based Study From the Shizuoka Kokuho Database

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shiori Nishimura ◽  
Hiraku Kumamaru ◽  
Shun Kohsaka ◽  
Satoshi Shoji ◽  
Eiji Nakatani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cumulative Incidence ◽  
Hospital Admissions ◽  
Laboratory Data ◽  
Administrative Claims ◽  
Cv Disease

Introduction: Recent large-scale clinical trials have shown that the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduces the risk of cardiovascular (CV) events, particularly heart failure (HF) hospitalizations, in type 2 diabetes mellitus (T2DM) patients with established CV disease. We aimed to assess (1) the incidence of HF admissions, and (2) the potential reduction in HF admissions with the further introduction of SGLT2i, in a contemporary large administrative claims database in Japan. Methods: We selected patients aged ≥40 years, without previous HF diagnosis, who newly initiated oral antidiabetics in Shizuoka Kokuho Database between 2013 and 2018. We estimated the 5-year cumulative incidence of hospitalization for HF, myocardial infarction (MI), and stroke, treating death as a competing risk. Among the subgroup of patients with laboratory data, we identified patients meeting the inclusion criteria for EMPA-REG OUTCOME (EMPA-REG) or DECLARE-TIMI 58 (DECLARE) regarding HbA1c, eGFR, and CV disease. We estimated the number of events that can be reduced if they benefited the same risk reduction from the trials. Results: Among 23,340 oral antidiabetic drug initiators (46.0% women, 21.9% ≥75 years old) included, 2.6% were initiated on SGLT2i. The 5-year cumulative incidences of hospitalization for HF, MI, and stroke were 5.4% (95% confidence interval: 4.9-5.9%), 1.9% (1.7-2.2%), and 6.1% (5.7-6.6%), respectively. Among 6192 patients with laboratory data, 651 (10.5%) and 2680 (43.3%) patients met the EMPA-REG-like and DECLARE-like criteria, respectively (Figure). The 5-year cumulative incidence among the 2849 patients meeting either of the criteria was estimated to decrease from 97.1 to 75.2 events via 75% adoption of SGLT2i. Conclusion: The burden of HF among Japanese T2DM patients was high, almost equivalent to stroke. Increased use of SGLT2i among patients with high CV risk may significantly reduce its disease burden.

Abstract 15516: Predicting Heart Failure Hospitalization in Type 2 Diabetes Mellitus: Validation of the TRS-HFDM Score in the ACCORD Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Malik Elharram ◽  
Thao Huynh ◽  
Jiayi Ni ◽  
João P Ferreira ◽  
Abhinav Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Risk Score ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Event Rates

Background: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk for developing heart failure (HF), and clinical models are needed to identify patients with a greater risk for HF hospitalization (HHF). The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM) was recently developed and validated to predict HHF in patients with T2DM in two large clinical trials (SAVOR-TIMI 53 and DECLARE-TIMI 58). We aimed to validate the TRS-HFDM in another cohort of patients with T2DM. Methods: We validated the TRS-HFDM score in 5,123 patients with T2DM for fatal or non-fatal HHF in the placebo arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes Study Group). The TRS-HFDM included: prior HF, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. We evaluated discrimination with the Harrell C index, and calibration by comparing observed event rates for HHF with predicted risk, and the Nam-D’Agostino statistic. Results: During a mean follow up of 4.8 years, 212 patients (4.14%) experienced at least one HHF. The mean age was 63 ±6.7 years, and 38% were female. The baseline hemoglobin A1C was 8.3%, and 36% were on insulin. The ACCORD patients had less comorbidities with a lower proportion of patients with renal dysfunction (8% vs. 16% vs. 17%), established cardiovascular disease (35% vs.79% vs. 41%) and pre-existing HF (5% vs. 13% vs. 10%) compared to patients enrolled in the SAVOR-TIMI 53 and DECLARE TIMI-58 trials respectively. In our cohort, the TRS-HFDM score predicted well HHF events with a Harrel C index of 0.78. The integer-based score was well calibrated, with the observed Kaplan-Meier HHF rates closely predicting the Kaplan-Meier event rates at the end follow up (Nam D`Agostino test: 65.39 (p<0.0001). Discussion: Our findings confirm the applicability of the TRS-HFDM in a large cohort of patients with T2DM with less high-risk features than the SAVOR-TIMI 53 and DECLARE-TIMI 58 populations. Future validation of this risk score in observational cohort studies is needed to evaluate its external validity in a general clinical setting.

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