Lower limb amputations: protection with GLP-1 receptor agonists rather than increased risk with SGLT2 inhibitors?

An increased risk of lower limb amputations (LLA) has been suspected with the use of sodium-glucose cotransporter type 2 inhibitors (SGLT2is) after the publication of CANVAS with canagliflozin compared with placebo. A more than twofold increase of the risk of LLA in SGLT2i users compared with patients treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been reported in a Scandinavian cohort observational study, yet other observational studies gave less alarming findings. Our meta-analysis of 12 retrospective cohorts revealed significant increase in LLA with a HR 1.15 (95% CI 1.05-1.24, I² 69%) when comparing SGLT2i users versus GLP-1RA users. However, another meta-analysis of observational studies showed no increased risk when SGLT2is were compared to dipeptidyl peptidase-4 inhibitors (DPP-4is) and some data showed a lower incidence of LLA in patients treated with GLP-1RAs compared to those treated with DPP-4is. When summarizing all available data with direct and indirect comparisons, a conclusion emerges that SGLT2is do not increase the risk of LLA but rather that GLP-1RAs may reduce such a risk.     

SGLT2 inhibitor/GLP-1 receptor agonists as first step monotherapy—evidence and implications

International Journal of Diabetes in Developing Countries -     

Relationship between epistaxis and hypertension: A cause and effect or coincidence?

Introduction

Epistaxis is the most common otorhinolaryngological emergency. Whether there is an association or cause and effect relationship between epistaxis and hypertension is a subject of longstanding controversy.

Objective

The aim of our study is to evaluate the relationship between epistaxis and hypertension.

Materials and methods

This study was conducted at Olaya Medical Center (Riyadh) during the period between May 2013 and June 2014. A total of 80 patients were divided into two groups: Group A consisted of 40 patients who presented with epistaxis, and Group B consisted of 40 patients who served as a control group. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed for all patients. Patients were followed up for a period of three months.

Results

Readings of blood pressure (BP) were similar between the two groups regarding BP at presentation, ABPM, and BP at three months. There was a higher number of attacks in patients with history of hypertension. There was highly significant positive correlation between number of attacks of epistaxis and BP readings. Systolic BP at presentation was higher in patients who needed more complex interventions such as pack, balloon or cautery than those managed by first aid.

Conclusion

We found no definite association between epistaxis and hypertension. Epistaxis was not initiated by high BP but was more difficult to control in hypertensive patients.     

Insulin and cardiovascular disease: biomarker or association?

In the 1980s prospective studies using whole populations suggested a relationship between insulin and cardiovascular disease, and these studies proposed that both metabolic and haemodynamic factors were associated with cardiovascular events. The initial analysis of the Paris Prospective Study (Diabetologia 19: 205–210), published in 1980, showed a positive correlation between insulin and cardiovascular events in healthy middle-aged policemen after a 5?year follow-up. In the Bedford Survey (Diabetologia 22: 79–84), also performed in the 1980s, a higher cardiovascular risk was demonstrated in diabetic patients and in those with borderline diabetes; however, in contrast to the Paris Prospective Study, insulin was negatively correlated to cardiovascular endpoints in the Bedford Survey. The initial enthusiasm for insulin as a cardiovascular risk marker was dampened when the 15?year follow-up data of the Paris Prospective Study (Diabetologia 34: 356–361) showed that the correlation between insulin and cardiovascular risk subsided with increased duration of follow-up. Despite the fact that hyperinsulinaemia was always strongly associated with other classical cardiovascular risk factors, univariate analyses usually failed to show a strong correlation between insulin and cardiovascular risk. The San Antonio Heart Study (Diabetologia 34: 416–422) performed in a bi-ethnic population that included a large proportion of Mexican-American participants again emphasised that insulin resistance may be the underlying factor associated with a cluster of metabolic and haemodynamic abnormalities. However, recently performed meta-analyses that included larger studies have not been able to confirm a critical role for insulin levels in cardiovascular risk. Indeed, it has been suggested that proinsulin or other factors may be better markers than insulin per se.     

Renin-angiotensin-aldosterone system blockade and renal protection: angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers?

Renal function is closely associated with cardiovascular risk, to the extent that even minor renal abnormalities, which are present in 10% of the general population, carry a greatly elevated risk of cardiovascular disease, target-organ damage and death. Reducing blood pressure by 20 mmHg or more in patients with severe hypertension (>160/100 mmHg) and advanced renal disease is sufficient to ensure a considerable reduction in proteinuria. In patients with less severe disease, however, blockade of the renin-angiotensin-aldosterone system (RAAS) is necessary to restore normal renal function. Clinical studies have shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), which both overcome the activity of angiotensin II, provide renoprotection in diabetics and non-diabetic populations. Which class of drugs is more effective remains a subject of debate, but the evidence favours ARBs for providing more effective renoprotection in patients at risk of diabetic nephropathy. The ARBs preserve renal haemodynamics and reduce progression to end-stage renal disease by around 25% in patients with overt nephropathy and prevent progression to overt disease by up to 70% in patients with mild renal impairment. The combination of ARBs and ACE inhibitors is even more protective, halving the number of patients with progression of renal impairment compared with either monotherapy. Long-term clinical studies now under way will help to establish the relative efficacies of the ARBs and ACE inhibitors and provide greater insight into the benefits of combination therapy.     

Managed care patient protection or provider protection? A qualitative assessment

PURPOSE: Opponents of managed care regulation allege that a patient's bill of rights, in reality, represents provider protections motivated by the desire to curtail the economic onslaught of managed care. This claim is assessed through a large qualitative study of state managed care patient protection laws. METHODS: State laws were reviewed and categorized, and regulators in each state were surveyed, to determine the pattern and content of relevant enactments as of the end of 2001. In 2002, six states were selected for in-depth case studies to reflect a range of market, demographic, and legal characteristics. In each state, 16 to 24 key informants were interviewed, including provider advocates, physician practices, health plan managers, regulators, patient advocates, and various industry observers. Additional interviews were conducted from a national perspective, for a total of 138 interviews. Interviews were semistructured, and interview notes were analyzed using qualitative techniques. RESULTS: These laws are directed primarily to patients' rights and only secondarily to providers' interests. Enactment of these laws was rarely attributed primarily to provider advocacy. Instead, providers aligned with consumers, or the impetus came from legislators or regulators. There was little evidence that these laws, collectively or individually, have had much effect on providers' economic concerns. Health plans are still free to form and shape networks as they see fit, subject to competitive constraints. Provider due process laws might suppress deselection to some extent, but most subjects thought these laws only marginally restrain health insurers from removing providers who they no longer want. CONCLUSION: Managed care patient protection laws do not advance a self-interested provider agenda that disables features of managed care that are beneficial to consumers. Instead, these laws appear to embody a convenient alignment of interests among providers, patients, and lawmakers.     

C-reactive protein and atherothrombosis: Cause or effect?

The complex relationship between the inflammatory response and vascular injury and repair is of major importance to the pathogenesis of cardiovascular disease. CRP is not only a strong marker for cardiovascular morbidity but a modulator that suppresses local and systemic thromboregulatory pathways. In the present review we address the question of whether CRP is involved in atherogenesis, in thrombosis, or in both components of the atherothrombotic process. While CRP is present in the atherosclerotic lesion, it is probably not pro-atherogenic and correlates only minimally with atherogenesis. Alas, CRP promotes thrombus formation and vascular occlusion. Thus, CRP is most likely not affecting atheroma build-up but rather the deleterious process of plaque vulnerability and thrombus formation. Dwelling into CRP mechanism of action may lead to the design of new diagnostic modalities that will add to the predictive value of CRP in identifying those patients at high cardiovascular risk. Furthermore, defining the mechanistic domain is the foundation to the cause–effect detection of possible therapeutic interventions to counter CRP morbid effects.