Blood pressure is an important determinant of the risk of macro- and microvascular vascular complications in patients with type 2 diabetes. Current European guidelines for the management of ...hypertension recommend lowering blood pressure in patients with type 2 diabetes to reduce the risk of cardiovascular events. The Action in Diabetes and Vascular DiseasePreterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (n = 11 140), is the first trial designed to address the issue of whether routine blood pressure lowering with the fixed combination of perindopril/indapamide is beneficial in patients with diabetes with a broad range of baseline blood pressure values. In addition, it aimed to determine if clinical benefit is achieved over and above that observed with background angiotension-converting enzyme inhibitor therapy. In the perindopril/indapamide arm, the reduction in blood pressure led to significant clinical benefits in patients with type 2 diabetes, irrespective of baseline blood pressure values, and subsequently improved mortality rates, and macro- and microvascular outcomes, beyond the improvements associated with patientsʼ existing antihypertensive therapies. ADVANCE is a robust well-designed trial, the results of which are directly applicable to current clinical practice. The ADVANCE study defines the relevant blood pressure goals for patients with type 2 diabetes who are at high risk of cardiovascular events and underscores the benefits of aggressive blood pressure reduction even in normotensive patients with diabetes. It is likely that these findings will have a significant impact on the management of patients with type 2 diabetes. In view of the evidence indicating that clinical benefits obtained with the perindopril/indapamide combination can be expected even in patients who are normotensive, vascular risk rather than initial blood pressure should be employed to determine appropriate treatment protocols in patients with type 2 diabetes.
The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in ...children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking.
The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years N = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male, and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ± 2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores.
A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity.
In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity.
Aims
Hyperkalaemia in heart failure patients limits use of cardioprotective renin–angiotensin–aldosterone system inhibitors (RAASi). Sodium zirconium cyclosilicate (ZS‐9) is a selective potassium ion ...trap, whose mechanism of action may allow for potassium binding in the upper gastrointestinal tract as early as the duodenum following oral administration. ZS‐9 previously demonstrated the ability to reduce elevated potassium levels into the normal range, with a median time of normalization of 2.2 h and sustain normal potassium levels for 28 days in HARMONIZE—a Phase 3, double‐blind, randomized, placebo‐controlled trial. In the present study we evaluated management of serum potassium with daily ZS‐9 over 28 days in heart failure patients from HARMONIZE, including those receiving RAASi therapies.
Methods and results
Heart failure patients with evidence of hyperkalaemia (serum potassium ≥5.1 mmol/L, n = 94) were treated with open‐label ZS‐9 for 48 h. Patients (n = 87; 60 receiving RAASi) who achieved normokalaemia (potassium 3.5–5.0 mmol/L) were randomized to daily ZS‐9 (5, 10, or 15 g) or placebo for 28 days. Mean potassium and proportion of patients maintaining normokalaemia during days 8–29 post‐randomization were evaluated. Despite RAASi doses being kept constant, patients on 5 g, 10 g, and 15 g ZS‐9 maintained a lower potassium level (4.7 mmol/L, 4.5 mmol/L, and 4.4 mmol/L, respectively) than the placebo group (5.2 mmol/L; P<0.01 vs. each ZS‐9 group); greater proportions of ZS‐9 patients (83%, 89%, and 92%, respectively) maintained normokalaemia than placebo (40%; P < 0.01 vs. each ZS‐9 group). The safety profile was consistent with previously reported overall study population.
Conclusion
Compared with placebo, all three ZS‐9 doses lowered potassium and effectively maintained normokalaemia for 28 days in heart failure patients without adjusting concomitant RAASi, while maintaining a safety profile consistent with the overall study population.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Smoking may lead to premature ageing, but the impact on the cardiovascular system and circulating proteins needs further investigation. In the present study, we aim to understand the impact of ...smoking on heart and vessels and circulating biomarkers of multiple domains including cardiovascular damage, premature ageing and cancer-related pathways.
The STANISLAS Cohort is a longitudinal familial cohort with detailed cardiovascular examination and biomarker assessment. This study included all the participants enrolled in the fourth visit of the STANISLAS Cohort for whom information on smoking habits was available (n = 1696). We assessed pulse wave velocity, intima-media thickness, echocardiographic parameters and a total of 460 proteins to study the association of circulating plasma proteins with smoking status (never vs. past vs. current smoking) while adjusting for potential confounders.
Current smokers were approximately 18 years younger but had higher left ventricular mass index (LVMi) and similar pulse wave velocity (PWV), carotid intima media thickness (cIMT), frequency of hypertension, diabetes and carotid plaques compared to the much older never smokers. After multivariate selection, 25 proteins were independently associated with current or past smoking. Current smoking was strongly associated with higher levels of EDIL-3, CCL11, TNFSF13B, KIT, and lower levels of IL-12B and PLTP (p < 0.0001) while past smoking was associated with FGF-21, CHIT1, and lower levels of CXCL10, IL1RL2 and RAGE (p < 0.01).
Current smoking is associated with signs of early onset of cardiovascular ageing and protein biomarkers that regulate inflammation, endothelial function, metabolism, oncological processes and apoptosis.
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•Cigarette smoking is associated with clinical markers of premature cardiovascular ageing.•Smokers had higher LVMi compared to much older non-smokers.•Current smoking was strongly associated with plasma proteins indicating inflammation, endothelial dysfunction and apoptosis.•Smokers had higher levels of EDIL-3, CCL11, TNFSF13B, KIT, and lower levels of IL-12B and PLTP compared to never smokers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Congestion is one of the main predictors of poor patient outcome in patients with heart failure. However, congestion is difficult to assess, especially when symptoms are mild. Although numerous ...clinical scores, imaging tools, and biological tests are available to assist physicians in ascertaining and quantifying congestion, not all are appropriate for use in all stages of patient management. In recent years, multidisciplinary management in the community has become increasingly important to prevent heart failure hospitalizations. Electronic alert systems and communication platforms are emerging that could be used to facilitate patient home monitoring that identifies congestion from heart failure decompensation at an earlier stage. This paper describes the role of congestion detection methods at key stages of patient care: pre-admission, admission to the emergency department, in-hospital management, and lastly, discharge and continued monitoring in the community. The multidisciplinary working group, which consisted of cardiologists, emergency physicians, and a nephrologist with both clinical and research backgrounds, reviewed the current literature regarding the various scores, tools, and tests to detect and quantify congestion. This paper describes the role of each tool at key stages of patient care and discusses the advantages of telemedicine as a means of providing true integrated patient care.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Aims
Stroke is often a devastating event among patients with heart failure with reduced ejection (HFrEF). In COMMANDER HF, rivaroxaban 2.5 mg b.i.d. did not reduce the composite of first ...occurrence of death, stroke, or myocardial infarction compared with placebo in patients with HFrEF, coronary artery disease (CAD), and sinus rhythm. We now examine the incidence, timing, type, severity, and predictors of stroke or a transient ischaemic attack (TIA), and seek to establish the net clinical benefit of treatment with low-dose rivaroxaban.
Methods and results
In this double-blind, randomized trial, 5022 patients who had HFrEF(≤40%), elevated natriuretic peptides, CAD, and who were in sinus rhythm were treated with rivaroxaban 2.5 mg b.i.d. or placebo in addition to antiplatelet therapy, after an episode of worsening HF. The primary neurological outcome for this post hoc analysis was time to first event of any stroke or TIA. Over a median follow-up of 20.5 (25th–75th percentiles 20.0–20.9) months, 150 all-cause stroke (127) or TIA (23) events occurred (ischaemic stroke in 82% and haemorrhagic stroke in 11% of stroke events). Overall, 47.5% of first-time strokes were either disabling (16.5%) or fatal (31%). Prior stroke, low body mass index, geographic region, and the CHA2DS2-VASc score were predictors of stroke/TIA. Rivaroxaban significantly reduced the primary neurological endpoint of all-cause stroke or TIA compared with placebo by 32% (1.29 events vs. 1.90 events per 100 patient-years), adjusted for the time from index HF event to randomization and stratified by geographic region (adjusted hazard ratio 0.68, 95% confidence interval 0.49–0.94), with a number needed to treat of 164 patients per year to prevent one stroke/TIA event. The principal safety endpoint of fatal bleeding or bleeding into a critical space, occurred at a similar rate on rivaroxaban and placebo (0.44 events vs. 0.55 events per 100 patient-years).
Conclusions
Patients with HFrEF and CAD are at risk for stroke or TIA in the period following an episode of worsening heart failure in the absence of atrial fibrillation. Most strokes are of ischaemic origin and nearly half are either disabling or fatal. Rivaroxaban at a dose of 2.5 mg b.i.d. reduced rates of stroke or TIA compared with placebo in this population.
Trial Registration
COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure); ClinicalTrials.gov NCT01877915.
There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported ...outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Racial Differences in Diabetic Cardiomyopathy Lopez, Jose; Liu, Yuxi; Butler, Javed ...
Journal of the American College of Cardiology,
07/2024, Volume:
84, Issue:
3
Journal Article
Peer reviewed
Diabetic cardiomyopathy (DbCM) increases risk of overt heart failure in individuals with diabetes mellitus. Racial and ethnic differences in DbCM remain unexplored.
The authors sought to identify ...racial and ethnic differences among individuals with type 2 diabetes mellitus, structural heart disease, and impaired exercise capacity.
The ARISE-HF (Aldolase Reductase Inhibitor for Stabilization of Exercise Capacity in Heart Failure) trial is assessing the efficacy of an aldose reductase inhibitor for exercise capacity preservation in 691 persons with DbCM. Baseline characteristics, echocardiographic parameters, and functional capacity were analyzed and stratified by race and ethnicity.
The mean age of the study participants was 67.4 years; 50% were women. Black and Hispanic patients had lower use of diabetes mellitus treatments. Black patients had poorer baseline ventricular function and more impaired global longitudinal strain. Overall, health status was preserved, based on Kansas City Cardiomyopathy Questionnaire scores, but reduced exercise capacity was present as evidenced by reduced Physical Activity Scale for the Elderly (PASE) scores. When stratified by race and ethnicity and compared with the entire cohort, Black patients had poorer health status, more reduced physical activity, and a greater impairment in exercise capacity during cardiopulmonary exercise testing, whereas Hispanic patients also displayed compromised cardiopulmonary exercise testing functional capacity. White patients demonstrated higher physical activity and functional capacity.
Racial and ethnic differences exist in baseline characteristics of persons affected by DbCM, with Black and Hispanic study participants demonstrating higher risk features. These insights inform the need to address differences in the population with DbCM. (Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy ARISE-HF; NCT04083339)
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