Heart Rate As a Biomarker in Heart Failure: Role of Heart Rate Lowering Agents.

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 ß-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.

Controversial Effects of Exogenous Testosterone on Cardiovascular Diseases.

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.

Effective Strategies in Reducing Rehospitalizations in Patients With Heart Failure.

Aging of the population and prolongation of the lives of patients with heart failure (HF) by advanced therapeutic innovations has led to an elevating number of patients who live with HF. The American Heart Association estimated that 5.1 million Americans were affected with HF in 2013 and approximately 23 million individuals were affected worldwide. Despite the improved management approaches, the mortality rate is still high; less than half of the patients with HF remain alive after 5 years of HF diagnosis and less than a quarter of them after 10 years. HF costs the nation a huge amount of money. The total cost comprises $34.4 billion each year, including the health care services, medications, and loss of productivity. Hospitalization is a common issue in HF, estimated as primary diagnosis in more than 1 million each year. Readmission after initial hospitalization is another concern in patients with HF. Around 25% will be readmitted in the next 30 days after hospital discharge, out of which only one-third is due to HF. It also costs the government an exhausting amount of money. The report of Medicare Payment Advisory Commission that was provided to the congress in 2008 showed that the expenses on HF readmissions were about $903. In this review, we intended to demonstrate the different strategies that could improve the readmission rates in patients with HF and ultimately decrease the health care payments. These strategies include evidence-based management programs, surgical therapy, risk factors adjustment, and disease monitoring.

Therapeutic Modulation of Aortic Stiffness.

Aortic stiffness (AS) is an important predictor of cardiovascular morbidity in humans. The present review discusses the possible pathophysiological mechanisms of AS and focuses on a survey of different therapeutic modalities for decreasing AS. The influence of several nonpharmacological interventions is described: decrease body weight, diet, aerobic exercise training, music, and continuous positive airway pressure therapy. The effects of different pharmacological drug classes on AS are also discussed: antihypertensive drugs-renin-angiotensin-aldosterone system drugs, beta-blockers, alpha-blockers, diuretics, and calcium channel blockers (CCBs)-advanced glycation end product cross-link breakers, statins, oral anti-diabetics, anti-inflammatory drugs, vitamin D, antioxidant vitamins, and endothelin-1 receptor antagonists. All of these have shown some effect in decreasing AS.

P-glycoprotein: a focus on characterizing variability in cardiovascular pharmacotherapeutics.

According to the report of Agency for Healthcare Research and Quality in 2008, drug-related adverse outcomes exceed 2.7 million events per year. Therefore, it is requisite to understand the etiologies of those unpleasant outcomes. Polypharmacy especially in the elderly is considered one of the major sources of drug-related side effects. The drug-related membrane transporters play an indispensable role in the pharmacokinetics, safety, and efficacy of the drugs. P-glycoprotein, also known as P-gp, is considered one of the core drug transporters in vivo. Since its discovery in 1976, P-gp gained a tremendous attention of researchers and clinicians. The core objective of this review is to highlight the clinical correlation between the P-gp and a number of cardiovascular drugs and to address the drug-drug interaction in case of using those cardiovascular drugs with P-gp-related drugs whether substrates, inhibitors, or inducers. Bearing in mind that P-gp is found in liver and intestine, as well as cytochrome P450, a strong association between the 2 systems is expected. Yet, plenty of the drugs that can behave as substrates to P-gp can act as substrates to CYP450 too. Consequently, probable drug-drug interaction can occur between drugs that work on both systems. In other words, whenever these classes of medications prescribed together cautious monitoring of drug's level and eventually dose adjustment might be necessary to avoid drug-drug interactions, failure of therapy, or drug toxicity; especially with the use of drugs that possess narrow therapeutic index like digoxin.

Glucagon-like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter Inhibitors for Treatment of T2DM.

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.

Intravenous Insulin Versus Conservative Management in Hypertriglyceridemia-Associated Acute Pancreatitis.

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.