F. Barkas

Spurious Electrolyte Disorders: A Diagnostic Challenge for Clinicians

Spurious electrolyte disorders refer to an artifactually elevated or decreased serum electrolyte values that do not correspond to their actual systemic levels. When a clinician is confronted with a case of electrolyte disturbance, the first question should be whether it is an artifact. Spurious electrolyte disorders (pseudohyponatremia, pseudohypernatremia, pseudohypokalemia, pseudohyperkalemia, pseudohypomagnesemia, pseudohypophosphatemia, pseudohyperphosphatemia, pseudohypocalcemia and pseudohypercalcemia) are not infrequently observed in clinical practice. The recognition that an electrolyte disturbance may be an artifact may prevent inappropriate therapeutic interventions that could potentially have unfavorable outcomes. Clinicians must be alert to the possibility of spurious laboratory abnormalities when faced with conflicting laboratory values or measurements that are discordant with the clinical presentation. Moreover, in the presence of conditions that predispose to spurious electrolyte disorders, the normal measured electrolyte levels should raise the suspicion that true electrolyte disorders may be present.

Cholesteryl ester transfer protein inhibitors: challenges and perspectives.

ABSTRACT Introduction: Cholesteryl ester transfer protein (CETP) inhibitors substantially increase the concentration of high-density lipoprotein cholesterol (HDL-C), which may have a possible beneficial effect for cardiovascular disease risk reduction. Areas covered: Current data regarding the effects of CETP inhibitors on cardiovascular disease risk and possible mechanisms for their effects and safety are presented in this review. Expert commentary: The first CETP inhibitor, torcetrapib, was discontinued because of increased off-target adverse effects (increased serum aldosterone and blood pressure levels). The development program of dalcetrapib and evacetrapib, which were not associated with increased blood pressure, was terminated due to futility (insufficient efficacy) concerning cardiovascular outcomes. Although the failure of torcetrapib has been attributed to specific off-target effects, there are some common characteristics between CETP inhibitors pointing to the possibility that certain adverse effects may be class-specific. The newer CETP inhibitors anacetrapib and TA-8995 have promising effects on lipid profile and metabolism (increase of HDL-C and reduction of both low-density lipoprotein cholesterol and lipoprotein (a) levels), but their cardiovascular effects and safety profile have not yet been confirmed in large outcome trials.

Dipeptidyl peptidase-4 inhibitors and protection against stroke: A systematic review and meta-analysis.

BACKGROUND Type 2 diabetes mellitus (T2DM) is associated with an increased risk of stroke and an unfavourable outcome following stroke. Apart from pioglitazone, glucose-lowering modalities have not been shown to protect against stroke. Nevertheless, there is evidence from experimental studies of potential neuroprotective effects with dipeptidyl peptidase (DPP)-4 inhibitors, especially if treatment starts before stroke. OBJECTIVE To perform a meta-analysis of available evidence regarding the risk of stroke in individuals taking DPP-4 inhibitors. METHODS All available data from prospective randomized placebo-controlled trials involving DPP-4 inhibitors in T2DM patients published up to December 2015 were considered. The included trials reported data on the incidence of stroke with a recruitment rate of at least 100 diabetes patients and a follow-up of at least 12 weeks. RESULTS A total of 19 small randomized clinical trials (RCTs) evaluating the efficacy and safety of gliptins (n=9278), along with three multicentre prospective double-blind placebo-controlled RCTs assessing cardiovascular outcomes as the primary endpoint and involving 36,395 T2DM patients, were included in the analysis. Pooled analysis of the small RCTs showed a non-significant trend towards benefit with DPP-4 inhibitors against stroke [odds ratio (OR): 0.639, 95% confidence interval (CI): 0.336-1.212; P=0.170]. In contrast, in the analysis of RCTs reporting on cardiovascular safety, there was no difference in the risk of stroke with gliptin treatment compared with a placebo (OR: 0.996, 95% CI: 0.850-1.166; P=0.958). CONCLUSION The promising data from experimental studies regarding cardioprotective gliptin-associated effects against stroke were not supported by available data from trials specifically looking at cardiovascular safety.

Effects of manidipine plus rosuvastatin versus olmesartan plus rosuvastatin on markers of insulin resistance in patients with impaired fasting glucose, hypertension, and mixed dyslipidemia.

Aim: To compare the effect of manidipine 20 mg plus rosuvastatin 10 mg versus olmesartan 20 mg plus rosuvastatin 10 mg on markers of insulin resistance in patients with mixed dyslipidemia, hypertension, and impaired fasting glucose (IFG). Methods: This study had a prospective, randomized, open-label, blinded endpoint (PROBE) design. A total of 40 patients with IFG, mixed dyslipidemia, and stage 1 hypertension were included. Following dietary intervention, patients were randomly allocated to rosuvastatin (10 mg/d) plus olmesartan (20 mg/d) or manidipine (20 mg/d). The primary end point was the between-group difference in changes in the Homeostasis Model Assessment Insulin Resistance (HOMA-IR) index following 3 months of treatment. Secondary end points included changes in fasting plasma glucose (FPG), fasting insulin levels, and glucosylated hemoglobin. Results: At the end of the 3-month treatment period, a significant increase in HOMA-IR index by 14% (from 2.4 [0.5-7.9] to 2.7 [0.5-5.2], P = .02 versus baseline) was seen in the olmesartan plus rosuvastatin group. On the contrary, no significant change in HOMA-IR index was observed in the manidipine plus rosuvastatin group (1.7 [0.5-5.2] to 1.7 [0.8-6.0], P = NS versus baseline, P = .04 versus olmesartan plus rosuvastatin group). An increase in fasting insulin levels was observed in the olmesartan plus rosuvastatin group (+8%, from 10.1 [2.0-29.6] to 10.9 [2.0-19.1] μU/mL, P < .05 versus baseline), while no significant change was seen in the manidipine plus rosuvastatin group (+3%, from 7.3 [2.0-17.6] to 7.5 [1.9-15.6] μU/mL, P = NS versus baseline, P = .02 versus olmesartan plus rosuvastatin group). Fasting plasma glucose and glycosylated hemoglobin did not change significantly in any group. Conclusion: Manidipine seems to ameliorate the possible statin-associated increase in insulin resistance as compared with olmesartan in patients with IFG, hypertension, and mixed dyslipidemia.

Beyond cholesterol reduction, the pleiotropic effects of statins: is their use in cancer prevention hype or hope?

Abstract “statins, which are prescribed to millions of patients for hypercholesterolemia treatment, have additional pleiotropic effects beyond cholesterol reduction that may include anticancer properties.”