Context and Objective Hypertriglyceridemia is implicated in ~5% of cases of acute pancreatitis. It is assumed that intravenous insulin is effective in lowering triglyceride (TG) concentrations in hypertriglyceridemia-associated acute pancreatitis (HAAP). However, the efficacy of intravenous insulin versus conservative management alone is not known. Design and Setting Charts of 106 patients who were admitted with HAAP and had TG concentrations >1000 mg/dL at admission were reviewed. Patients who received intravenous insulin for at least 8 hours were included in the intravenous insulin group, while the rest were considered to have received conservative management. We compared the change in TG concentrations from baseline in the 2 groups. Results Fifty-one patients received intravenous insulin while 55 patients were managed conservatively. Baseline TG concentrations were higher in the intravenous insulin group (median [25th, 75th percentile] 3307 [2106, 4425] mg/dL vs 2304 [1416, 2720] mg/dL; P < 0.001). The TG concentrations declined rapidly in both groups, reaching below 1000 mg/dL by day 3 and < 500 mg/dL by day 4. TG concentrations in the intravenous insulin group had decreased by 69% and 85% on days 2 and 4, respectively. The fall in the conservative management group was 63% and 79%, which was not statistically different than the change in the intravenous insulin group. Conclusion Our results show that intravenous insulin did not result in a more rapid fall in TG compared with conservative treatment in patients with HAAP. Fasting and intravenous fluids were effective in lowering TG concentrations rapidly, with no further contribution from insulin.
Context Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes. Objective Assist in the prescribing decision regarding severity of illness and risk for adverse events. Design Meta-analysis of the major CVOT and previous meta-analyses. Main Outcome Measures Six trials of GLP-1 RA (51 762 subjects) and 4 trials of SGLT2i (33 457 subjects) showed both drug classes reduced MACE and CVD versus controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: relative rate [rr] MACE 1.09, 95% confidence interval [CI] 0.97, 1.22, P = ns; rr CVD 1.04, 95% CI 0.87, 1.24, P = ns). Hospitalization for heart failure (HHF) improved with SGLT2i (rr 0.68, CI 0.61, 0.76, P < 0.001) but not with GLP-1 RA, (rr 0.93, CI 0.86,1.03, P = ns). Meta-regression suggested benefits of the SGLT2i on CVD and HHF were accentuated with the underlying rate of MACE in the cohort (i.e., >10 events/1000pt*year). GLP-1 RA and SGLT2i showed reduction in renal outcomes (GLP-1 RA rr 0.83, CI 0.75, 0.91, p ≤ 0.001, SGLT2i rr 0.67, CI 0.57, 0.79, P < 0.001) without a preferential difference (GLP-1 RA vs SGLT2i, rr 1.24, CI 0.95, 1.61, P = ns; relative difference (rd) 0.005, CI -0.011, 0.021, P = ns). Serious adverse events for SGLT2i were mycotic genital infections in women (number needed to harm [NNH] = 13 and diabetic ketoacidosis NNH = 595. Gastrointestinal intolerance was the serious adverse event in the GLP1-RA class (NNH = 35). Conclusion GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and renal outcomes. SGLT2i have advantages over GLP-1 RA in reduction in HHF.
Heart failure (HF) is a common clinical condition affecting more than 5.8 million people in the United States, it remains the leading cause of death in the United States and worldwide. Ongoing challenges for biomarker identification include the need for objective assessment, measurement precision, and meaningful replication. Biomarkers not only serve as traditional predictors of prognosis, they can also help to identify high-risk patients who need closer monitoring and more aggressive therapy; therefore, we reviewed the use of heart rate (HR) as a biomarker in HF both of diagnostic and prognostic values, in addition, to being easily detected. HR is a determinant of myocardial oxygen demand, coronary blood flow, and myocardial performance and is central to the adaptation of cardiac output to metabolic needs. Increased HR is known to predict adverse outcome in the general population and in patients with chronic HF. Part of the ability of HR to predict risk is related to the forces driving it, namely, neurohormonal activation. We reviewed therapies, which slow the HR like β-blockers and ivabradine (a drug that is a pure HR-reducing agent), and all the clinical studies suggest the benefit of these drugs in the management of HF, and increasing evidence suggests HR as a biomarker of both diagnostic and prognostic values in HF.
The use of testosterone (T) among men aged 40 years or older was increased more than 3 times from 0.81% in 2001 to 2.91% in 2011. Until recently, the majority of the studies did not show any increased cardiovascular (CV) risk by using T in male patients with hypogonadism. What is more, some studies had observed a protective effect of using T against CV diseases. However, in 2010, a randomized clinical trial (RCT) was intended to study the advantage of T gel in older men with limitations in mobility; the study was stopped due to unexpected high prevalence of CV adverse outcome. These findings were confirmed by 2 other studies published in November of 2013 and January of 2014. Consequently, the Food and Drug Administration (FDA) had announced in January 2014 that it will reassess the safety of those treatments. Meanwhile, the agency had not reached to a definitive conclusion that FDA-approved testosterone therapy raises the risk of stroke, heart attack, or death. A report released in the broadcast of the NBC Nightly News in September of this year that the FDA says "there's little evidence that T boosting drugs taken by millions of American men are actually effective." NBC notes that the agency also pointed out that it was not convinced that they carry serious risk either. "The condition has been marketed as low 'T', and the medications are offered to help with low sex drive and fatigue among some men," notes NBC. The European Medicines Agency EMA's Pharmacovigilance Risk Assessment Committee has also responded to the concern of potential CV adverse outcomes associated with the use of T, and they have concluded in their October meeting of this year that the use of T in men who do not produce enough T raises the risk of heart diseases. In our review, we highlighted the association between exogenous T and major adverse CV outcomes. Additionally, we focused on the interplay between exogenous T and some endocrine abnormalities such as diabetes mellitus type 2, metabolic syndrome, dyslipidemia, and obesity.
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