Background-Chronic kidney disease is a risk factor for cardiovascular disease, increasing all-cause mortality. Some evidence suggests that endothelial dysfunction is present in the early stages of renal insufficiency, but no data exist about its possible role in the progression of renal disease. Thus, we prospectively evaluated the effect of endothelial function on estimated glomerular filtration rate (eGFR) in essential hypertension. Methods and Results-We enrolled 500 never-treated uncomplicated hypertensive subjects with serum creatinine Յ1.5 mg/dL. Endothelial function was measured by strain-gauge plethysmography during intra-arterial infusion of acetylcholine and sodium nitroprusside.
The GLP-1 receptor agonist exenatide has been approved for adjunctive treatment of type 2 diabetes. Continuous GLP-1 infusion improves endothelial function in vivo; no evidence about a beneficial effect of exenatide on vascular function has been published. The aim of our observational study was to evaluate whether exenatide would improve brachial artery function evaluated by the flow mediated dilation (FMD) technique, compared with glimepiride, in subjects with type 2 diabetes. FMD time course was assessed by ultrasound, after 5 min forearm ischaemia, at baseline and after 16-week treatment. At the end of the study FMD was significantly higher in subjects who assumed exenatide compared with glimepiride (9.1 ± 3.6 vs. 5.6 ± 1.0, p = 0.01). Even if limited by the small number of studied subjects, who were not matched in the two treatment groups, this research study represents the first FMD evidence suggesting that chronic administration of exenatide improves arterial dilation.
Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34(+) and CD34(+)KDR(+) progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p < 0.05), IIT did not reduce the cumulative incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21-1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41-19.5, p < 0.02). Baseline CD34(+)KDR(+) were higher in rs753482AA (166.2 ± 154.0 × 10(6) events) than in rs753482AC+CC (63.1 ± 26.9 × 10(6) events, p < 0.01). At the end of the study, the highest circulating CD34(+)KDR(+) were found in IIT rs753482AA (246.9 ± 194.0 × 10(6) events) while the lowest levels were found in SC rs753482AC+CC (70.9 ± 45.0 × 10(6) events). IIT did not decrease the cumulative incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.
Insulin resistance and endothelial dysfunction are associated with heart failure (HF). Our objective was to investigate whether endothelial dysfunction and insulin resistance are independent predictors of incident HF and if a possible interaction exists between them. We enrolled 705 white never-treated hypertensives. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. During the follow-up [median: 117 months (range: 31–211)], we documented 223 new cases of HF (3.3 events/100 patient-years). We stratified the study population into progressors and non-progressors; progressors showed an older age and a higher prevalence of females, as well as higher mean values of baseline glucose, insulin, homeostasis model assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP), whereas the estimated glomerular filtration rate (e-GFR) and endothelium-dependent vasodilation were lower. In the multiple Cox regression analysis, serum hs-CRP (HR = 1.362, (95% CI = 1.208–1.536), HOMA (HR = 1.293, 95% CI = 1.142–1.465), maximal acetylcholine (Ach)-stimulated forearm blood flow (FBF) (100% increment, HR = 0.807, 95% CI = 0.697–0.934), and e-GFR (10 mL/min/1.73 m2 increment, HR = 0.552, 95% CI = 0.483–0.603) maintained an independent association with incident HF. HOMA and endothelial dysfunction interact between them in a competitive manner (HR = 6.548, 95% CI = 4.034–10.629), also showing a mutual effect modification. Our findings demonstrate that both endothelial dysfunction and HOMA are independent and strong predictors of incident HF in hypertensives, these two risk factors interact between them with a competitive mechanism.
Pharmacological treatment of heart failure with reduced ejection fraction has undergone considerable development in recent years. Type 2 sodium–glucose co–transporter inhibitors represent the most recent class of drugs that has been shown to reduce hospital admissions for heart failure and deaths from cardiovascular causes and have immediately entered in the most recent international guidelines for the treatment of HFrEF patients. The objective of this survey, which involved various cardiologists from Puglia, Molise and Abruzzo, was to analyze the clinical characteristics and therapeutic associations of patients in whom SGLT2i therapy was prescribed. Into the REINFORCE project, each of the cardiologists participating in the survey was asked to provide anonymised data of patients who were initiated on SGLT2i therapy. Each cardiologist provided information on the main clinical and therapeutic characteristics of the patients. Data relating to 788 patients on SGLT2i therapy (98.8% dapagliflozin) were analysed. 71% of patients were male, with a mean age of 69.5 years. Approximately 53.5% of the cases had an ischemic heart failure aetiology, 73% had arterial hypertension and 40.6% had type 2 diabetes mellitus. Of these, 83.9% had HFrEF, the 12.3% from HFmrEF and 3.9% from HFpEF. 38.8% of patients had presented an episode of hospitalization for heart failure (in the previous 6 months). At the time of the visit, 23.2% of patients had a serum creatinine value >1.3 mg/dL. 47% of patients were in NYHA Class I–II, while 53% had an advanced class (NYHA III). The analysis of concomitant drug therapies using SGLT2i showed that: 93.4% of the patients were on therapy with a renin angiotensin system inhibitor (40.5% ACEI/ARBs and 52.8% ARNI), 65.9% were on MRA and 91.5% beta blockers. 86.1% of patients were on concomitant diuretic therapy with furosemide.
Conclusions
Data from the REINFORCE study provide real–world data to help understand the characteristics of heart failure patients prescribed SGLT2i therapy. The data show safety and tolerability of the therapies provided also in the ARNI–SGLT2i association which, associated with efficacy documented in the trials, would suggest to favor this association as soon as possible.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.