scholarly journals Interplay between worsening kidney function and cardiovascular events in patients with type 2 diabetes: an analysis from the ACCORD trial

2021 ◽  
Vol 9 (1) ◽  
pp. e002408
Author(s):  
João Pedro Ferreira ◽  
Diana Ferrao ◽  
Patrick Rossignol ◽  
Faiez Zannad ◽  
Abhinav Sharma ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Kidney Function ◽  
Cardiovascular Events ◽  
Large Population ◽  
Joint Modeling ◽  
Cardiovascular Death ◽  
High Cardiovascular Risk ◽  
Increased Risk

IntroductionPatients with type 2 diabetes (T2D) have an increased risk of worsening kidney function (WKF) over time compared with patients without diabetes. Data evaluating the inter-relation between WKF, cardiovascular risk, and clinical events are scarce. We aim to study the association of WKF with subsequent cardiovascular events and the probabilities of transition from WKF to hospitalization or death according to patients’ risk. We have used a large population of patients with T2D and a high cardiovascular risk enrolled in the Action to Control Cardiovascular Risk in Diabetes Study.Research design and methodsTime-updated, joint, and multistate modeling were used. WKF was defined as an estimated glomerular filtration rate (eGFR) decline greater than 40% from baseline. A total of 10 251 patients were included, of whom 1213 (11.8%) presented WKF over a median (percentile25–75) follow-up time of 5.0 (4.1–5.7) years.ResultsPatients who experienced WKF were slightly older, more frequently women, and had longer diabetes duration. Patients experiencing WKF, regardless of baseline kidney function, had a higher risk of subsequent cardiovascular events, including the composite of cardiovascular death or hospitalization for heart failure (HHF), with ≈2-fold higher risk. Joint modeling showed that renal function deterioration frequently occurs even among patients who did not experience a cardiovascular event. In multistate models, patients with a medium-high cardiovascular risk (compared with those with a low cardiovascular risk) are at higher risk of HHF or cardiovascular death first (HR=4.76, 95% CI 3.63 to 6.23) than of WKF first (HR=1.37, 95% CI 1.21 to 1.56); remarkably, the risk of cardiovascular death or HHF is highest after a WKF event (HR=6.20, 95% CI 2.71 to 14.8).ConclusionsIn patients with T2D and a high cardiovascular risk, WKF occurs in more than 10% of patients and is independently associated with risk of subsequent cardiovascular events, irrespective of baseline eGFR. Preventing serious WKF and the transition from WKF to HHF or cardiovascular death is an important objective of future trials.Trial registration numberNCT00000620.

scholarly journals Association Between Circulating GDF‐15 and Cardio‐Renal Outcomes and Effect of Canagliflozin: Results From the CANVAS Trial

2021 ◽  
Author(s):  
Taha Sen ◽  
Jingwei Li ◽  
Brendon L. Neuen ◽  
Clare Arnott ◽  
Bruce Neal ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Protective Effect ◽  
Cox Regression ◽  
Cardiovascular Death ◽  
High Cardiovascular Risk ◽  
Cardiovascular Assessment ◽  
Glomerular Filtration Rate Decline ◽  
End Stage

Background Studies have suggested that sodium glucose co‐transporter 2 inhibitors exert anti‐inflammatory effects. We examined the association of baseline growth differentiation factor‐15 (GDF‐15), a marker of inflammation and cellular injury, with cardiovascular events, hospitalization for heart failure (HF), and kidney outcomes in patients with type 2 diabetes in the CANVAS (Canagliflozin Cardiovascular Assessment Study) and determined the effect of the sodium glucose co‐transporter 2 inhibitor canagliflozin on circulating GDF‐15. Methods and Results The CANVAS trial randomized 4330 people with type 2 diabetes at high cardiovascular risk to canagliflozin or placebo. The association between baseline GDF‐15 and cardiovascular (non‐fatal myocardial infarction, non‐fatal stroke, cardiovascular death), HF, and kidney (40% estimated glomerular filtration rate decline, end‐stage kidney disease, renal death) outcomes was assessed using multivariable adjusted Cox regression models. During median follow‐up of 6.1 years (N=3549 participants with available samples), 555 cardiovascular, 129 HF, and 137 kidney outcomes occurred. Each doubling in baseline GDF‐15 was significantly associated with a higher risk of cardiovascular (hazard ratio [HR], 1.2; 95% CI, 1.0‒1.3), HF (HR, 1.5; 95% CI, 1.2‒2.0) and kidney (HR, 1.5; 95% CI, 1.2‒2.0) outcomes. Baseline GDF‐15 did not modify canagliflozin’s effect on cardiovascular, HF, and kidney outcomes. Canaglifozin treatment modestly lowered GDF‐15 compared with placebo; however, GDF‐15 did not mediate the protective effect of canagliflozin on cardiovascular, HF, or kidney outcomes. Conclusions In patients with type 2 diabetes at high cardiovascular risk, higher GDF‐15 levels were associated with a higher risk of cardiovascular, HF, and kidney outcomes. Canagliflozin modestly lowered GDF‐15, but GDF‐15 reduction did not mediate the protective effect of canagliflozin.

scholarly journals A higher non-severe hypoglycaemia rate is associated with an increased risk of subsequent severe hypoglycaemia and major adverse cardiovascular events in individuals with type 2 diabetes in the LEADER study

Diabetologia ◽  
2021 ◽  
Author(s):  
Simon R. Heller ◽  
Milan S. Geybels ◽  
Ahmed Iqbal ◽  
Lei Liu ◽  
Lily Wagner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Severe Hypoglycaemia ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Post Hoc Analysis ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Post Hoc

Abstract Aims/hypothesis Hypoglycaemia is a common side effect of insulin and some other antihyperglycaemic agents used to treat diabetes. Severe hypoglycaemia has been associated with adverse cardiovascular events in trials of intensive glycaemic control in type 2 diabetes. The relationship between non-severe hypoglycaemic episodes (NSHEs) and severe hypoglycaemia in type 2 diabetes has been documented. However, an association between more frequent NSHEs and cardiovascular events has not been verified. This post hoc analysis of the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial aimed to confirm whether there is an association between NSHEs and severe hypoglycaemic episodes in individuals with type 2 diabetes. In addition, the possible association between NSHEs and major adverse cardiac events (MACE), cardiovascular death and all-cause mortality was investigated. Methods LEADER was a double-blind, multicentre, placebo-controlled trial that found that liraglutide significantly reduced the risk of MACE compared with the placebo. In this post hoc analysis, we explored, in all LEADER participants, whether the annual rate of NSHEs (defined as self-measured plasma glucose <3.1 mmol/l [56 mg/dl]) was associated with time to first severe hypoglycaemic episode (defined as an episode requiring the assistance of another person), time to first MACE, time to cardiovascular death and time to all-cause mortality. Participants with <2 NSHEs per year were used as reference for HR estimates. Cox regression with a time-varying covariate was used. Results We demonstrate that there is an association between NSHEs (2–11 NSHEs per year and ≥12 NSHEs per year) and severe hypoglycaemic episodes (unadjusted HRs 1.98 [95% CI 1.43, 2.75] and 5.01 [95% CI 2.84, 8.84], respectively), which was consistent when baseline characteristics were accounted for. Additionally, while no association was found between participants with 2–11 NSHEs per year and adverse cardiovascular outcomes, higher rates of NSHEs (≥12 episodes per year) were associated with higher risk of MACE (HR 1.50 [95% CI 1.01, 2.23]), cardiovascular death (HR 2.08 [95% CI 1.17, 3.70]) and overall death (HR 1.80 [95% CI 1.11, 2.92]). Conclusions/interpretation The analysis of data from the LEADER trial demonstrated that higher rates of NSHEs were associated with both a higher risk of severe hypoglycaemia and adverse cardiovascular outcomes in individuals with type 2 diabetes. Therefore, irrespective of the cause of this association, it is important that individuals with high rates of hypoglycaemia are identified so that the potentially increased risk of cardiovascular events can be managed and steps can be taken to reduce NSHEs. Trial registration ClinicalTrials.gov (NCT01179048). Graphical abstract

scholarly journals Disease overarching mechanisms that explain and predict outcome of patients with high cardiovascular risk: rationale and design of the Berlin Long-term Observation of Vascular Events (BeLOVE) study

2019 ◽  
Author(s):  
Bob Siegerink ◽  
Joachim Weber ◽  
Michael Ahmadi ◽  
Kai-Uwe Eckardt ◽  
Frank Edelmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Cardiovascular Events ◽  
Target Organ Damage ◽  
Organ Damage ◽  
High Cardiovascular Risk

AbstractBackgroundCardiovascular disease (CVD) is the leading cause of premature death worldwide. Effective and individualized treatment requires exact knowledge about both risk factors and risk estimation. Most evidence for risk prediction currently comes from population-based studies on first incident cardiovascular events. In contrast, little is known about the relevance of risk factors for the outcome of patients with established CVD or those who are at high risk of CVD, including patients with type 2 diabetes. In addition, most studies focus on individual diseases, whereas less is known about disease overarching risk factors and cross-over risk.AimThe aim of BeLOVE is to improve short- and long-term prediction and mechanistic understanding of cardiovascular disease progression and outcomes in very high-risk patients, both in the acute as well as in the chronic phase, in order to provide the basis for improved, individualized management.Study designBeLOVE is an observational prospective cohort study of patients of both sexes aged >18 in selected Berlin hospitals, who have a high risk of future cardiovascular events, including patients with a history of acute coronary syndrome (ACS), acute stroke (AS), acute heart failure (AHF), acute kidney injury (AKI) or type 2 diabetes with manifest target-organ damage. BeLOVE includes 2 subcohorts: The acute subcohort includes 6500 patients with ACS, AS, AHF, or AKI within 2-8 days after their qualifying event, who undergo a structured interview about medical history as well as blood sample collection. The chronic subcohort includes 6000 patients with ACS, AS, AHF, or AKI 90 days after event, and patients with type 2 diabetes (T2DM) and target-organ damage. These patients undergo a 6-8 hour deep phenotyping program, including detailed clinical phenotyping from a cardiological, neurological and metabolic perspective, questionnaires including patient-reported outcome measures (PROMs)as well as magnetic resonance imaging. Several biological samples are collected (i.e. blood, urine, saliva, stool) with blood samples collected in a fasting state, as well as after a metabolic challenge (either nutritional or cardiopulmonary exercise stress test). Ascertainment of major adverse cardiovascular events (MACE) will be performed in all patients using a combination of active and passive follow-up procedures, such as on-site visits (if applicable), telephone interviews, review of medical charts, and links to local health authorities. Additional phenotyping visits are planned at 2, 5 and 10 years after inclusion into the chronic subcohort.Future perspectiveBeLOVE provides a unique opportunity to study both the short- and long-term disease course of patients at high cardiovascular risk through innovative and extensive deep phenotyping. Moreover, the unique study design provides opportunities for acute and post-acute inclusion and allows us to derive two non-nested yet overlapping sub-cohorts, tailored for upcoming research questions. Thereby, we aim to study disease-overarching research questions, to understand crossover risk, and to find similarities and differences between clinical phenotypes of patients at high cardiovascular risk.

scholarly journals Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

Diabetes Care ◽  
2022 ◽  
Author(s):  
Avivit Cahn ◽  
Stephen D. Wiviott ◽  
Ofri Mosenzon ◽  
Erica L. Goodrich ◽  
Sabina A. Murphy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Cox Regression ◽  
Cardiovascular Death ◽  
Atherosclerotic Cardiovascular Disease ◽  
Baseline Hba1c ◽  
Renal Outcomes ◽  
Increased Risk ◽  
Hba1c Levels

OBJECTIVE Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models. RESULTS In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06–1.19], 1.08 [1.04–1.13], and 1.17 [1.11–1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction &gt; 0.05). CONCLUSIONS Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c &lt;7%.

scholarly journals High cardiovascular risk of patients with type 2 diabetes is only partially attributed to angiographic burden of atherosclerosis

2020 ◽  
Vol 17 (5) ◽  
pp. 147916412095361
Author(s):  
Simone Battermann ◽  
Andrea Milzi ◽  
Rosalia Dettori ◽  
Kathrin Burgmaier ◽  
Nikolaus Marx ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Quantitative Coronary Angiography ◽  
High Cardiovascular Risk ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Angiographic Data ◽  
Artery Disease ◽  
Stable Cad

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events and present more severe coronary artery disease (CAD). The Gensini and COURAGE scores are established angiographic instruments to assess CAD severity, which may also predict future cardiovascular risk. However, it is unclear if these scores are able to depict the increased risk of patients with T2DM and stable CAD (T2DM-SAP). Methods: We performed quantitative coronary angiography and assessed the Gensini and COURAGE scores in 124 patients with T2DM-SAP. Angiographic data were compared to patients with stable angina without T2DM (Non-DM-SAP, n = 74), and to patients with acute coronary syndrome and T2DM (T2DM-ACS, n = 53). Results: T2DM-SAP patients had similar Gensini and COURAGE-scores compared to Non-DM-SAP-patients (Gensini: 14.44 ± 27.34 vs 11.49 ± 26.99, p = 0.465; COURAGE: 3.48 ± 4.49 vs 3.60 ± 4.72, p = 0.854). In contrast, T2DM-SAP patients had significantly lower Gensini (14.44 ± 27.34 vs 30.94 ± 48.74, p = 0.003) and lower COURAGE (3.48 ± 4.49 vs 5.30 ± 4.63, p = 0.016) scores compared to T2DM-ACS-patients. Conclusion: Both the Gensini and the COURAGE score fail to predict the high cardiovascular risk of patients with T2DM-SAP. Therefore, these scores should be used with caution in the assessment of future risk of patients with T2DM. However, among T2DM-ACS patients, both scores are increased, reflecting the high cardiovascular risk in this patient population.

scholarly journals Interconnection of the level of uric acid at risk of development of type 2 diabetes mellitus on FINDRISC scale in women moderate and high cardiovascular risk

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
I Komir ◽  
G Isayeva ◽  
N Emelyanova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Cardiovascular Risk ◽  
Communicable Disease ◽  
Public Institution ◽  
High Cardiovascular Risk ◽  
Increased Risk

Abstract Aim To establish a relationship between the level of uric acid and the risk of development of type 2 diabetes mellitus (DM2) on the FINDRISC scale in women of moderate and high cardiovascular risk. Material and methods 103 women (average age (58,39±11,09) years) with moderate and high cardiovascular risk were examined. Women were divided into groups depending on age: 1 group of age to 50 years old, 2 groups with the age of 50–60 years old, 3 groups more than 60 years. The risk of developing the DM2 in the next 10 years was evaluated using the FINDRISC questionnaire. The level of uric acid was determined by a photometric substantial method. For statistical analysis, SPSSIBM, version 19.0. Results It has been established that women, in general, had an increased risk of developing DM2 (11,0 [7,0–14,0] points). The level of uric acid in them was (295,0 [230,0–380,5] μmol/l). In the distribution of women by age, there was no probable difference in uric acid levels (257,0 [249,0–257,5]; 256,0 [210,7–353,3]; 295,0 [231,0–362,5] μmol/l; p&gt;0,05). However, the risk of developing DM2 has probably grown in women depending on age (4,00 [0,25–9,25]; 9,50 [7,00–14,00]; 14,50 [12,50–16,00] points). Uric acid correlated with the FINDRISC scale at the significance level (0,489, p=0,05). However, with the distribution of women, depending on age, we observed the interconnection of uric acid with the risk of developing DM2 at the level of significance only in women 2 groups (0,604, p=0,01). Conclusions The level of uric acid is interacting with the risk of developing DM2 on the FINDRISC scale in women of moderate and high cardiovascular risk at the age of 50–60 years. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Government Institution “L.T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine”, Department of Chronic Non-communicable Disease Prevention

scholarly journals Disease overarching mechanisms that explain and predict outcome of patients with high cardiovascular risk: rationale and design of the Berlin Long-term Observation of Vascular Events (BeLOVE) study

2019 ◽  
Author(s):  
Bob Siegerink ◽  
Joachim Weber ◽  
Michael Ahmadi ◽  
Kai-Uwe Eckardt ◽  
Frank Edelmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Cardiovascular Events ◽  
Target Organ Damage ◽  
Organ Damage ◽  
High Cardiovascular Risk

Background: Cardiovascular disease (CVD) is the leading cause of premature death worldwide. Effective and individualized treatment requires exact knowledge about both risk factors and risk estimation. Most evidence for risk prediction currently comes from population-based studies on first incident cardiovascular events. In contrast, little is known about the relevance of risk factors for the outcome of patients with established CVD or those who are at high risk of CVD, including patients with type 2 diabetes. In addition, most studies focus on individual diseases, whereas less is known about disease overarching risk factors and cross-over risk. Aim: The aim of BeLOVE is to improve short- and long-term prediction and mechanistic understanding of cardiovascular disease progression and outcomes in very high-risk patients, both in the acute as well as in the chronic phase, in order to provide the basis for improved, individualized management. Study design: BeLOVE is an observational prospective cohort study of patients of both sexes aged >18 in selected Berlin hospitals, who have a high risk of future cardiovascular events, including patients with a history of acute coronary syndrome (ACS), acute stroke (AS), acute heart failure (AHF), acute kidney injury (AKI) or type 2 diabetes with manifest target-organ damage. BeLOVE includes 2 subcohorts: The acute subcohort includes 6500 patients with ACS, AS, AHF, or AKI within 2-8 days after their qualifying event, who undergo a structured interview about medical history as well as blood sample collection. The chronic subcohort includes 6000 patients with ACS, AS, AHF, or AKI 90 days after event, and patients with type 2 diabetes (T2DM) and target-organ damage. These patients undergo a 6-8 hour deep phenotyping program, including detailed clinical phenotyping from a cardiological, neurological and metabolic perspective, questionnaires including patient-reported outcome measures (PROMs)as well as magnetic resonance imaging. Several biological samples are collected (i.e. blood, urine, saliva, stool) with blood samples collected in a fasting state, as well as after a metabolic challenge (either nutritional or cardiopulmonary exercise stress test). Ascertainment of major adverse cardiovascular events (MACE) will be performed in all patients using a combination of active and passive follow-up procedures, such as on-site visits (if applicable), telephone interviews, review of medical charts, and links to local health authorities. Additional phenotyping visits are planned at 2, 5 and 10 years after inclusion into the chronic subcohort. Future perspective: BeLOVE provides a unique opportunity to study both the short- and long-term disease course of patients at high cardiovascular risk through innovative and extensive deep phenotyping. Moreover, the unique study design provides opportunities for acute and post-acute inclusion and allows us to derive two non-nested yet overlapping sub-cohorts, tailored for upcoming research questions. Thereby, we aim to study disease-overarching research questions, to understand crossover risk, and to find similarities and differences between clinical phenotypes of patients at high cardiovascular risk.

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