The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics: Analysis of the CREDENCE trial

Heart failure is prevalent in those with type 2 diabetes and chronic kidney disease, and is associated with significant mortality and morbidity. In the CREDENCE trial, canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In the current analysis we sought to determine whether the effect of canagliflozin on HHF/CV death differed in subgroups defined by key baseline participant characteristics. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Canagliflozin was associated with a reduction in the relative risk of HHF/CV death regardless of age, sex, history of heart failure or CV disease, and the use of loop diuretics or glucagon-like peptide-1 receptor agonists (all p_interaction > .114). The absolute benefit of canagliflozin was greater in those at highest baseline risk, such as those with CV disease (50 fewer events/1000 patients treated over 2.5 years vs. 20 fewer events in those without CV disease) or advanced kidney disease (estimated glomerular filtration rate [eGFR] 30–45 mL/min/1.73m²: 61 events prevented/1000 patients treated over 2.5 years vs. 23 events in eGFR 60–90 mL/min/1.73m²). Canagliflozin consistently reduces the proportional risk of HHF/CV death across a broad range of subgroups with greater absolute benefits in those at highest baseline risk.     

Kidney,Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria: A CREDENCE Secondary Analysis

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Association of Interleukin-1β-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR–RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.     

The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease

Endothelium plays a crucial role in the maintenance of vascular tone and structure. Endothelial dysfunction is known to precede overt coronary artery disease. A number of cardiovascular risk factors, as well as metabolic diseases and systemic or local inflammation cause endothelial dysfunction. Nitric oxide (NO) is one of the major endothelium derived vaso-active substances whose role is of prime importance in maintaining endothelial homeostasis. Low levels of NO are associated with impaired endothelial function. Asymmetric dimethylarginine (ADMA), an analogue of L-arginine, is a naturally occurring product of metabolism found in human circulation. Elevated levels of ADMA inhibit NO synthesis and therefore impair endothelial function and thus promote atherosclerosis. ADMA levels are increased in people with hypercholesterolemia, atherosclerosis, hypertension, chronic heart failure, diabetes mellitus and chronic renal failure. A number of studies have reported ADMA as a novel risk marker of cardiovascular disease. Increased levels of ADMA have been shown to be the strongest risk predictor, beyond traditional risk factors, of cardiovascular events and all-cause and cardiovascular mortality in people with coronary artery disease. Interventions such as treatment with L-arginine have been shown to improve endothelium-mediated vasodilatation in people with high ADMA levels. However the clinical utility of modifying circulating ADMA levels remains uncertain.     

A clinical risk score for atrial fibrillation in a biracial prospective cohort (from the Atherosclerosis Risk in Communities [ARIC] study)

A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study; however, the applicability of this risk score, derived using data from white patients, to predict new-onset AF in nonwhites is uncertain. Therefore, we developed a 10-year risk score for new-onset AF from risk factors commonly measured in clinical practice using 14,546 subjects from the Atherosclerosis Risk In Communities (ARIC) study, a prospective community-based cohort of blacks and whites in the United States. During 10 years of follow-up, 515 incident AF events occurred. The following variables were included in the AF risk score: age, race, height, smoking status, systolic blood pressure, hypertension medication use, precordial murmur, left ventricular hypertrophy, left atrial enlargement, diabetes, coronary heart disease, and heart failure. The area under the receiver operating characteristics curve (AUC) of a Cox regression model that included the previous variables was 0.78, suggesting moderately good discrimination. The point-based score developed from the coefficients in the Cox model had an AUC of 0.76. This clinical risk score for AF in the Atherosclerosis Risk In Communities cohort compared favorably with the Framingham Heart Study's AF (AUC 0.68), coronary heart disease (CHD) (AUC 0.63), and hard CHD (AUC 0.59) risk scores and the Atherosclerosis Risk In Communities CHD risk score (AUC 0.58). In conclusion, we have developed a risk score for AF and have shown that the different pathophysiologies of AF and CHD limit the usefulness of a CHD risk score in identifying subjects at greater risk of AF.     

Alcohol Abuse and Cardiac Disease

Background

Understanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.

Procedural Variations in Performing Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction

Multiple variations exist in performing a primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) among various cardiologists. These variations range from the choice of peripheral access artery (radial vs femoral), performance or time of complete angiography including left ventriculography, and nonculprit vessel angiography before or after intervening on the culprit vessel. The reasons for such variations include emphasis on door-to-balloon time, knowledge of cardiac anatomy before proceeding with pPCI, physician expertise, and the level of comfort with radial approach. Over the last 2 decades, the field of interventional cardiology has changed dynamically leading to marked improvements in the clinical outcomes of patients with STEMI. This includes upstreaming of pPCI along with technical advancements ranging from radial artery catheterization to culprit lesion–guided approach. Increased comfort with use of radial access approach by cardiologists and availability of multiuse guide catheters would both reduce door-to-balloon time and enable complete coronary angiography before performance of percutaneous coronary intervention. There are no clear guidelines or consensus dictating on cardiologists a correct sequence of action during STEMI, or even suggesting what the preferred approach is. Lack of guidelines results in a substantive variation in methodology. This review aims to highlight and to better understand the variations in the current practice, and to emphasize the advantages as well as the disadvantages of each approach. It is also perhaps a call out for guidelines that direct cardiologists to the best practice.