Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Current management of chronic kidney disease in type-2 diabetes-A tiered approach: An overview of the joint Association of British Clinical Diabetologists and UK Kidney association (ABCD-UKKA) guidelines.

A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD) and people with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD). Despite advances in care over the recent decades, most people with CKD and type 2 diabetes are likely to die of CVD before developing ESKD. Hyperglycaemia and hypertension are modifiable risk factors to prevent onset and progression of CKD and related CVD. People with type 2 diabetes often have dyslipidaemia and CKD per se is an independent risk factor for CVD, therefore people with CKD and type 2 diabetes require intensive lipid lowering to reduce burden of CVD. Recent clinical trials of people with type 2 diabetes and CKD have demonstrated a reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy and kidney death) with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonist finerenone and glucagon-like peptide 1 receptor agonists. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the management of hyperglycaemia, hyperlipidaemia and hypertension in adults with type 2 diabetes and CKD. This 2024 abbreviated updated guidance summarises the recommendations and the implications for clinical practice for healthcare professionals who treat people with diabetes and CKD in primary, community and secondary care settings

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Long-term risk prediction after major lower limb amputation: 1-year results of the PERCEIVE study

Background: Decision-making when considering major lower limb amputation is complex and requires individualized outcome estimation. It is unknown how accurate healthcare professionals or relevant outcome prediction tools are at predicting outcomes at 1-year after major lower limb amputation. Methods: An international, multicentre prospective observational study evaluating healthcare professional accuracy in predicting outcomes 1 year after major lower limb amputation and evaluation of relevant outcome prediction tools identified in a systematic search of the literature was undertaken. Observed outcomes at 1 year were compared with: healthcare professionals' preoperative predictions of death (surgeons and anaesthetists), major lower limb amputation revision (surgeons) and ambulation (surgeons, specialist physiotherapists and vascular nurse practitioners); and probabilities calculated from relevant outcome prediction tools. Results: A total of 537 patients and 2244 healthcare professional predictions of outcomes were included. Surgeons and anaesthetists had acceptable discrimination (C-statistic = 0.715), calibration and overall performance (Brier score = 0.200) when predicting 1-year death, but performed worse when predicting major lower limb amputation revision and ambulation (C-statistics = 0.627 and 0.662 respectively). Healthcare professionals overestimated the death and major lower limb amputation revision risks. Consultants outperformed trainees, especially when predicting ambulation. Allied healthcare professionals marginally outperformed surgeons in predicting ambulation. Two outcome prediction tools (C-statistics = 0.755 and 0.717, Brier scores = 0.158 and 0.178) outperformed healthcare professionals' discrimination, calibration and overall performance in predicting death. Two outcome prediction tools for ambulation (C-statistics = 0.688 and 0.667) marginally outperformed healthcare professionals. Conclusion: There is uncertainty in predicting 1-year outcomes following major lower limb amputation. Different professional groups performed comparably in this study. Two outcome prediction tools for death and two for ambulation outperformed healthcare professionals and may support shared decision-making

Ezetimibe; More Than a Low Density Lipoprotein Cholesterol Lowering Drug? An Update After 4 Years

Ezetimibe (EZE), a selective inhibitor of intestinal cholesterol absorption, is mostly used in combination with statins across various patient populations. Besides its low-density lipoprotein cholesterol (LDL-C) lowering, EZE exerts different effects on several other variables. In an earlier review, we discussed the effects of EZE on lipid parameters other than LDL-C [e.g. C-reactive protein (CRP) levels, insulin sensitivity and endothelial function]. In the present review, we consider recent evidence regarding these topics as well as data reporting novel EZE actions. EZE may protect from cholelithiasis and non-alcoholic fatty liver disease (NAFLD) and appears as an effective lipid-lowering treatment option for human-immunodeficiency virus (HIV)-positive patients, transplant recipients and children with familial hypercholesterolaemia (FH). Studies with EZE that raised concern about its effects on atherosclerosis are also discussed. The potential clinical benefit of these actions with respect to vascular events and overall mortality remains to be established in appropriately designed trials