Phosphate imbalance in patients with heart failure.

Patients with heart failure often exhibit electrolyte abnormalities, such as hyponatremia or hypokalemia/hyperkalemia. Although not as common as the other electrolyte disturbances observed in patients with heart failure, phosphate imbalance is also of high importance in this population. The aim of this review is to present the mechanisms of low or high phosphate serum levels in patients with heart failure and its role in the pathogenesis and progression of heart dysfunction. Hypophosphatemia in patients with heart failure may be the result of co-existing electrolyte and acid-base abnormalities, pharmacological treatments, decreased intestinal absorption or secondary to sympathetic nervous system activation and co-morbidities, such as diabetes mellitus or heavy alcohol consumption. Hypophosphatemia can affect multiple organ systems including the cardiovascular system. Depletion of phosphate can lead to ventricular arrhythmias and elimination of ATP synthesis, resulting in reversible myocardial dysfunction. Hyperphosphatemia, observed mainly in patients with chronic kidney failure, is also associated with cardiac hypertrophy, which may worsen cardiac contractility and heart failure. Studies have also shown an association of high-normal serum phosphate levels with vascular and valvular calcification. Therefore, serum phosphate imbalances may exhibit a causal role in the pathogenesis and progression of heart failure.

Effects of 12 months of treatment with disease-modifying anti-rheumatic drugs on low and high density lipoprotein subclass distribution in patients with early rheumatoid arthritis: a pilot study.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have increased cardiovascular risk. The aim of the present study was the assessment of low density lipoprotein (LDL) and high density lipoprotein (HDL) subclass distribution in patients with early RA (ERA, n = 30) compared with age- and sex-matched healthy subjects (n = 30), as well the effect of treatment for 12 months with the disease-modifying anti-rheumatic drugs (DMARDs) methotrexate and prednisone in this distribution. METHOD: LDL and HDL subclass distribution was determined using a polyacrylamide gel-tube electrophoresis method. RESULTS: ERA patients exhibited increased levels of inflammatory markers and high disease activity score. ERA patients had higher serum levels of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG) whereas their serum HDL cholesterol (HDL-C) levels were significantly lower compared with controls. ERA patients exhibited significantly higher plasma levels of small dense LDL-C (sdLDL-C), leading to a significantly decreased mean LDL diameter. ERA patients had significantly decreased small HDL particles (HDL-3) concentration whereas serum levels of large HDL particles (HDL-2) did not differ compared with controls. Treatment with DMARDs resulted in a significant decrease in inflammatory markers and disease activity, along with a significant increase in HDL-C serum levels. The concentration of sdLDL-C did not change significantly during treatment. We observed a significant increase in the levels of large HDL-2 whereas the concentration of small HDL-3 did not significantly change. CONCLUSIONS: Patients with ERA have increased sdLDL-C levels and decreased HDL-C levels because of decreased concentration of the small HDL-3 subclass. The administration of DMARDs induced a significant increase in HDL-C levels, which was attributed to the increase in large HDL-2 serum concentration.

Increased plasma visfatin concentration is a marker of an atherogenic metabolic profile.

BACKGROUND AND AIMS: Visfatin is associated with atherosclerosis-related diseases. We assessed in non-diabetic individuals the association of plasma visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis-related metabolic variables. METHODS AND RESULTS: When study population (n = 179, age 49 ± 11 years) was divided according to visfatin tertiles, the 10-year CVD Framingham risk scores were significantly increased in the top visfatin tertile. We observed a positive association between visfatin tertiles with waist circumference and blood pressure, as well as with total cholesterol and triglyceride levels, but not with apolipoprotein C-III, fibrinogen or pre-beta1 high density lipoprotein (HDL). The percentage of large HDL subclasses was significantly lower and the percentage of small HDL subclasses over the HDL-C concentration was significantly higher in the top visfatin tertile compared with the other tertiles. The atherogenic small dense low density lipoprotein subclasses (sdLDL-C) were significantly increased in the top visfatin tertile compared with the lower tertiles. High sensitivity C-reactive protein (hsCRP) concentration was significantly increased in the top visfatin tertile compared with the lower tertiles. Although age and sex distribution did not differ between visfatin tertiles, the simultaneous adjustment for these parameters attenuated the significance of the differences observed in sdLDL-C and hsCRP levels. Similarly, after adjustment for hsCRP or waist circumference, only triglycerides and blood pressure levels, as well as the distribution of HDL subclasses, remained significantly different between visfatin tertiles. CONCLUSIONS: Our results support a role for visfatin in the detection of subjects with many metabolic abnormalities, which result in increased CVD risk.

Lysis syndrome during therapy of visceral leishmaniasis.

INTRODUCTION: Lysis syndrome is a constellation of metabolic disorders usually seen after the initiation of chemotherapy for rapidly proliferating malignancies (tumor lysis syndrome). Reported herein is a tumor lysis-like syndrome after the initiation of anti-infective therapy for visceral leishmaniasis. PATIENTS AND METHODS: Ten consecutive patients with visceral leishmaniasis were administered liposomal amphotericin B. Levels of serum uric acid, phosphate, creatinine, blood urea nitrogen, potassium, calcium, and magnesium were evaluated prior to as well as 4 and 30 days following the initiation of treatment. RESULTS: During the 4th post-treatment day significant increases in the levels of serum uric acid, phosphate, creatinine, and blood urea nitrogen were seen, while the levels of calcium, potassium, and magnesium were not significantly altered. Patients were treated by hydration, urine alkalization, and administration of allopurinol as needed. A recovery of metabolic abnormalities was recorded 1 month later, although some patients had evidence of residual injury. CONCLUSION: A lysis syndrome may complicate the treatment of visceral leishmaniasis. Awareness of this complication can lead to the initiation of prophylactic treatment as well as to early recognition and management of this syndrome in susceptible patients.

Effect of rosuvastatin monotherapy or in combination with fenofibrate or ω-3 fatty acids on lipoprotein subfraction profile in patients with mixed dyslipidaemia and metabolic syndrome.

BACKGROUND: Raised triglycerides (TG), decreased high-density lipoprotein cholesterol (HDL-C) levels and a predominance of small dense low density lipoproteins (sdLDL) are characteristics of the metabolic syndrome (MetS). OBJECTIVE: To compare the effect of high-dose rosuvastatin monotherapy with moderate dosing combined with fenofibrate or ω-3 fatty acids on the lipoprotein subfraction profile in patients with mixed dyslipidaemia and MetS. METHODS: We previously randomised patients with low-density lipoprotein cholesterol (LDL-C) > 160 and TG > 200 mg/dl to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or ω-3 fatty acids 2 g/day (Rω group, n = 30). In the present study, only patients with MetS were included (24, 23 and 24 in the R, RF and Rω groups respectively). At baseline and after 12 weeks of treatment, the lipoprotein subfraction profile was determined by polyacrylamide 3% gel electrophoresis. RESULTS: The mean LDL size was significantly increased in all groups. This change was more prominent with RF than with other treatments in parallel with its greater hypotriglyceridemic capacity (p < 0.05 compared with R and Rω). A decrease in insulin resistance by RF was also noted. Only RF significantly raised HDL-C levels (by 7.7%, p < 0.05) by increasing the cholesterol of small HDL particles. The cholesterol of larger HDL subclasses was significantly increased by R and Rω. CONCLUSIONS: All regimens increased mean LDL size; RF was the most effective. A differential effect of treatments was noted on the HDL subfraction profile.

Rosuvastatin treatment is associated with an increase in insulin resistance in hyperlipidaemic patients with impaired fasting glucose.

AIM OF THE STUDY: The increase in physician-reported diabetes following rosuvastatin treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin study has raised concerns whether this statin exerts a detrimental effect on glucose metabolism. We assessed the effect of rosuvastatin treatment across dose range on glucose homeostasis in hyperlipidaemic patients with impaired fasting glucose (IFG), who are at high risk to develop diabetes mellitus. METHODS: The medical records of 72 hypelipidaemic patients with IFG on rosuvastatin 10 (RSV10 group), 20 (RSV20 group) and 40 mg/day (RSV40 group) were reviewed. The median follow up was 12.4 weeks. At the first visit, prior to rosuvastatin prescription and at the latest visit, serum lipid profile and indices of glucose metabolism, including fasting glucose, insulin and HOmeostasis Model Assessment (HOMA(IR)) index levels, were assessed. RESULTS: Rosuvastatin treatment improved lipid profile and was associated with a dose-dependent significant increase in HOMA(IR) values by 25.4%, 32.3% and 44.8% at the dose of 10, 20 and 40 mg/day (p < 0.01 for all, p < 0.05 for the comparison between groups), respectively, mirrored by correspondent increase in plasma insulin levels [by 21.7%, 25.7% and 46.2% in the RSV10, RSV20 and RSV40 group (p < 0.001 for all) respectively]. Baseline HOMA(IR) levels was the most important contributor (R(2) = 68.1%, p < 0.001), followed by the dose of rosuvastatin treatment (R(2) = 23.7%, p < 0.01), in a model that explained 91.8% of the variability in HOMA(IR) increase. CONCLUSION: In patients with IFG and hyperlipidaemia, rosuvastatin treatment was associated with a dose-dependent increase in insulin resistance.

Long-term exposure to medium-dose glucocorticoid therapy associates with hypertension in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) associates with increased cardiovascular morbidity and mortality that is due to both traditional and novel cardiovascular risk factors. Hypertension (HT), one of the most common risk factors for cardiovascular disease, is highly prevalent in RA. The effects of long-term glucocorticoid (GC) therapy on blood pressure have not been established yet. This study examined whether GC exposure associates with HT in patients with RA. METHODS: Four hundred consecutive RA patients with detailed clinical and laboratory assessments were categorized into three groups according to GC exposure: no or limited exposure (N/L-E); a low-dose (< 7.5 mg) long-term exposure (LD/LT-E); and medium-dose (> or = 7.5 mg) long-term exposure (MD/LT-E). The association of GC exposure with HT was evaluated using logistic regression analysis. RESULTS: HT was more prevalent in the MD/LT-E group (84.7%) than the LD/LT-E or N/L-E groups (70.7 and 67.3%, respectively, P = 0.028). Logistic regression revealed increased odds for HT when comparing MD/LT-E with N/L-E, after adjustment for HT risk factors [odds ratio (OR) = 2.57, 95% CI 1.01-6.56, P = 0.049] and RA disease characteristics (OR = 3.64, 95% CI: 1.36-9.77, P = 0.01). CONCLUSIONS: MD/LT GC exposure associates with a very high prevalence of HT. This appears to be independent of other risk factors for HT or of channelling bias due to disease severity, even though the latter cannot be excluded given the cross-sectional nature of our study. RA patients in this GC exposure group should be particularly targeted for early identification and aggressive management of HT.

The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome.

OBJECTIVE: We assessed the effect of orlistat and fenofibrate, alone or in combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre-beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS). METHODS: Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL subfractions were determined using a polyacrylamide gel tube electrophoresis method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay. RESULTS: We observed a significant change of high-density lipoprotein cholesterol (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were significantly increased and small HDL-C levels were significantly reduced with O administration. In F group we observed a significant increase of small HDL-C levels. No significant change of large or small HDL-C levels was observed with combination treatment. We observed a significant increase of pre-beta1-HDL levels in all groups, which was significantly greater in OF group compared with O or F monotherapy. CONCLUSION: OF combination increased the antiatherogenic pre-beta1-HDL levels in overweight and obese patients with MetS. Furthermore, OF combination counterbalanced the reduction of small HDL-C levels observed with orlistat monotherapy.

Serum uric acid is independently associated with hypertension in patients with rheumatoid arthritis.

Hypertension (HT) is highly prevalent in rheumatoid arthritis (RA). Serum uric acid (SUA) has been associated with HT in the general population. The mutual exclusion of gout and RA, and the systemic inflammatory component of RA may alter this association in this patient population. We explored a potential association between SUA levels and HT in RA and evaluated whether this association is independent of HT risk factors, RA characteristics and relevant drugs. A total of 400 consecutive RA patients were assessed. SUA and complete biochemical profile were measured. Demographic, HT-related factors, RA characteristics and drugs were assessed as potential covariates. Results were analysed using binary logistic models to test the independence of the association between SUA and HT. SUA levels were higher in hypertensive compared to normotensive RA patients (5.44+/-1.6 mg dl(-1) (323.57+/-95.17 micromol l(-1)) vs 4.56+/-1.1 mg dl(-1) (271.23+/-65.43 micromol l(-1)), P<0.001). When adjusted for HT risk factors, renal function, RA characteristics, non-steroidal anti-inflammatory drugs, oral prednisolone, cyclosporine, leflunomide and low-dose aspirin, the odds of being a hypertensive RA patient per 1 mg dl(-1)(59.48 micromol l(-1)) SUA increase were significantly increased: OR=1.59 (95% CI: 1.21-2.1, P=0.001). This was also significant for the subgroup of patients who were not on diuretics (OR=1.5, 95% CI: 1.1-2.05; P=0.011). This cross-sectional study suggests that SUA levels are independently associated with HT in RA patients. Prospective longitudinal studies are needed to confirm and further explore the causes and implications of this association.

Effects of sibutramine and orlistat on mood in obese and overweight subjects: a randomised study.

BACKGROUND AND AIM: Intentional weight loss results in improvement in mood. Very few data exist regarding the effects of sibutramine on the mood of obese and overweight patients in general clinical samples. Moreover, no study has evaluated the effects of orlistat treatment on mood. The purpose of our study was to assess the effects of sibutramine and orlistat on mood in obese and overweight subjects. METHODS AND RESULTS: Sixty obese and overweight women were divided into three groups. The first group (n=20) received a low-calorie diet and sibutramine 10mg; the second group (n=20) received a low-calorie diet and orlistat 120 mg three times a day, and the third group received only the low-calorie diet. CONCLUSION: A psychiatric assessment was performed with the Hamilton Depression Rating Scale (HAMD) before and after 3 months of treatment. In all the groups a statistically significant decrease in HAMD scores was observed. However, the decrease in the sibutramine group was greater compared to that observed in the two other groups (P<0.01). These results suggest that sibutramine treatment may improve mood more than diet alone or orlistat therapy in a general clinical sample of obese patients.

Do statins have an antiarrhythmic activity?

Sudden cardiac death, which is mainly associated with the presence of life-threatening ventricular arrhythmias, is a common 'killer' among patients with coronary artery disease. Moreover, atrial fibrillation is the most common arrhythmia encountered in the clinical practice. The beneficial effect of statins on cardiovascular morbidity and mortality is well-established, while the exact role of this class of drugs against arrhythmias remains unclear. This review discusses the effect of statin treatment on arrhythmias that are commonly seen in the clinical setting. The underlying pathophysiological mechanisms are also overviewed. Compelling evidence from the majority of the studies reviewed shows that statins exhibit a protective effect against the occurrence of ventricular arrhythmias and atrial fibrillation.

SGLT2 inhibitors and the kidney: Effects and mechanisms.

AIMS: Numerous clinical trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors exert a favorable effect on the indices of renal function (albuminuria, glomerular filtration rate decline over time) and the incidence of hard renal endpoints such as renal death or time to initiation of renal replacement therapy. MATERIALS AND METHODS: In this review, we describe in detail the evidence regarding the nephroprotective mechanisms of SGLT2 inhibitors and describe the risk factors that may predispose to the development of acute kidney injury in patients receiving these drugs. RESULTS: Although the impact of these drugs on renal hemodynamics seems to represent the most important renoprotective mechanism of action, many other effects of these compounds, including beneficial effects on metabolism and blood pressure, have been proposed to contribute to the observed clinical benefit. CONCLUSIONS: SGLT2 inhibitors clearly act beneficially in terms of kidney function with many proposed mechanisms.

Gitelman syndrome: an analysis of the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities.

Gitelman syndrome is the most common inherited tubular disease resulting from mutations of the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter in the early distal convoluted tubules. The review presents the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities observed in patients with Gitelman syndrome. The syndrome is usually characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Additionally, increased chloride excretion and renin/aldosterone levels, hypophosphatemia (occasionally), hyponatremia (rarely) and glucose intolerance/insulin resistance have been reported. The knowledge of the pathophysiologic mechanisms is useful for the treatment of patients with Gitelman syndrome as well as for the understanding of other tubular diseases.

SGLT2 inhibitors-induced electrolyte abnormalities: An analysis of the associated mechanisms.

AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that affect serum electrolytes levels. The aim of this review is the detailed presentation of the associated mechanisms of the SGLT2 inhibitors-induced electrolyte abnormalities. MATERIALS AND METHODS: Eligible trials and relevant articles published in PubMed (last search in July 2017) are included in the review. RESULTS: SGLT2 inhibitors induce small increases in serum concentrations of magnesium, potassium and phosphate. The small increase in serum phosphate concentration may result in reduced bone density and increased risk of bone fractures, mainly seen with canagliflozin, but recent meta-analyses did not show increased risk of bone fractures with SGLT2 inhibitors. CONCLUSION: The increases in serum electrolytes levels may play a role in the cardiovascular protection that has been recently reported with empagliflozin and canagliflozin.

The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome.

BACKGROUND: Increased concentration of small dense LDL cholesterol (sdLDL-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are considered as emerging cardiovascular risk factors and are commonly encountered in subjects with metabolic syndrome (MetS). OBJECTIVE: The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients (body mass index>28 kg/m(2)) with MetS. METHODS: Patients (n=89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200mg/day (F group) or both (OF group) for 6 months. RESULTS: Significant reductions of sdLDL-C levels were observed in all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C levels (p<0.05) together with a greater increase in LDL particle diameter (p<0.05) compared with group O. Total plasma Lp-PLA(2) activity significantly decreased in all treatment groups. The reduction of Lp-PLA(2) was more pronounced with OF administration compared with each monotherapy (p<0.05). CONCLUSION: Orlistat and fenofibrate exhibited favorable effects on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients with MetS. Importantly, combination treatment had a more favorable effect on these risk factors.

Excess body weight and risk of first-ever acute ischaemic non-embolic stroke in elderly subjects.

In a population-based case-control study we assessed the association between obesity and acute ischaemic/non-embolic stroke. A total of 163 patients aged older than 70 years (88 men and 75 women) admitted due to a first-ever-in-a-lifetime acute ischaemic/non-embolic stroke and 166 volunteers (87 men and 79 women) without a history of cardiovascular disease were included. The association of stroke with body mass index (BMI) or waist circumference (WC) was determined by multivariate logistic regression modelling after adjusting for potential confounding factors. Overweight and obesity were more prevalent amongst stroke patients compared to controls. Subjects with a BMI > or = 30 kg/m2 had 2.5-times higher odds to suffer an acute ischaemic/non-embolic stroke compared to subjects within the lowest BMI category of 18.5-20.9 kg/m2. Analysis of interaction showed that in the presence of overweight and/or obesity (classified as a BMI > or = 25 kg/m2 and/or a WC > 102 cm in men and > 88 cm in women) the inverse relationship between HDL cholesterol and ischaemic/non-embolic stroke was negated. Excess weight is associated with an increased risk of acute ischaemic/non-embolic stroke in elderly individuals independently of concurrent metabolic derangements. Moreover, in the presence of obesity, HDL cholesterol loses its protective effect against ischaemic stroke.

Increased plasma levels of visfatin/pre-B cell colony-enhancing factor in obese and overweight patients with metabolic syndrome.

BACKGROUND: Visfatin [pre-B cell colony- enhancing factor (PBEF)] is a cytokine highly expressed in visceral fat that exhibits insulin-mimetic properties. However, its role in insulin-resistant states, such as in metabolic syndrome (MetS), remains largely unknown. OBJECTIVE: To investigate the possible differences of plasma visfatin levels between obese and overweight subjects with and without MetS. DESIGN AND PATIENTS: Plasma visfatin concentrations were measured with enzyme-linked immunosorbent assay (ELISA) in 28 overweight and obese [body mass index (BMI)>28 kg/m2] subjects with Mets and 28 age- and sex-matched overweight and obese (BMI>28 kg/m2) individuals without MetS (control group). RESULTS: Patients with MetS exhibited significantly elevated waist circumference (WCR ) values, higher blood pressure readings, higher fasting glucose and triglyceride concentrations as well as lower levels of HDL cholesterol (HDL-C) compared with controls. Total and LDL cholesterol (LDL-C) concentrations did not differ significantly between the two groups. Plasma visfatin concentrations were significantly higher in subjects with MetS compared with controls [27 (16- 65) ng/ml vs 19 (10-47) ng/ml, p<0.05]. The same results were observed even after adjustment for age, sex and BMI. Plasma visfatin levels were positively correlated with age (r=0.32, p<0.05), WCR (r=0.31, p<0.05), triglyceride (r=0.59, p<0.01) and glucose (r=0.33, p<0.05) levels and were negatively correlated with HDL-C levels (r=-0.38, p<0.05). Multiple linear regression analysis revealed similar results. CONCLUSION: Plasma visfatin levels are increased in overweight and obese subjects with MetS compared with those individuals who do not fulfil the criteria for the diagnosis of MetS.

Use of intravenous fluids/solutions: a narrative review.

OBJECTIVE: Intravenous fluids are broadly categorized into colloids and crystalloids. The aim of this review is to present under a clinical point of view the characteristics of intravenous fluids that make them more or less appropriate either for maintaining hydration when enteral intake is contraindicated or for treating hypovolemia. METHODS: We considered randomized trials and meta-analyses as well as narrative reviews evaluating the effects of colloids or crystalloids in patients with hypovolemia or as maintenance fluids published in the PubMed and Cochrane databases. RESULTS: Clinical studies have not shown a greater clinical benefit of albumin solutions compared with crystalloid solutions. Furthermore, albumin and colloid solutions may impair renal function, while there is no evidence that the administration of colloids reduces the risk of death compared with resuscitation with crystalloids in patients with trauma, burns or following surgery. Among crystalloids, normal saline is associated with the development of hyperchloremia-induced impairment of kidney function and metabolic acidosis. On the other hand, the other commonly used crystalloid solution, the Ringer's Lactate, has certain indications and contraindications. These matters, along with the basic principles of the administration of potassium chloride and bicarbonate, are meticulously discussed in the review. CONCLUSIONS: Intravenous fluids should be dealt with as drugs, as they have specific clinical indications, contraindications and adverse effects.

Pharmacological management of diabetic dyslipidemia.

INTRODUCTION: Diabetes mellitus is associated with increased cardiovascular disease (CVD) risk. Areas covered: Main goal of hypolipidemic treatment in diabetic patients is low-density lipoprotein cholesterol (LDL-C) lowering with the use of statins. Addition of ezetimibe is useful in diabetic patients who cannot achieve their LDL-C target. However, many diabetic patients have increased residual CVD risk, which is mainly attributed to high triglycerides and low high-density lipoprotein (HDL-C) values. The addition of fenofibrate targets these variables and possibly reduces residual CVD risk, but a possible beneficial effect has been shown only in a pre-specified subgroup analysis in patients with high triglycerides and low HDL-C values. The newer proprotein convertase subtilisin/kexin type 9 inhibitors lower substantially LDL-C levels, but data from specifically designed trials in diabetic patients are not currently available. Although the cholesterol ester transfer protein (CETP) inhibitors have shown harmful effects or lack of efficacy in completed clinical trials, the newer CETP inhibitors have promising effects on lipid profile and carbohydrate metabolism, but their effects on CVD risk and safety profile have not been assessed. Expert commentary: Clinicians have a range of pharmacological options to reduce the CVD risk of diabetic patients.

MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment.

BACKGROUND: Patients with moderate to severe hypothyroidism and mainly patients with myxedema may exhibit reduced sodium levels (<135 mmol/L). SUMMARY: The aim of this short review is the presentation of the mechanisms of hyponatremia and of the available data regarding its implications and treatment in patients with hypothyroidism. Hypothyroidism is one of the causes of hyponatremia, thus thyroid-stimulating hormone determination is mandatory during the evaluation of patients with reduced serum sodium levels. The main mechanism for the development of hyponatremia in patients with chronic hypothyroidism is the decreased capacity of free water excretion due to elevated antidiuretic hormone levels, which are mainly attributed to the hypothyroidism-induced decrease in cardiac output. However, recent data suggest that the hypothyroidism-induced hyponatremia is rather rare and probably occurs only in severe hypothyroidism and myxedema. Other possible causes and superimposed factors of hyponatremia (e.g. drugs, infections, adrenal insufficiency) should be considered in patients with mild/moderate hypothyroidism. Treatment of hypothyroidism and fluid restriction are usually adequate for the management of mild hyponatremia in patients with hypothyroidism. Patients with possible hyponatremic encephalopathy should be urgently treated according to current guidelines. CONCLUSIONS: Severe hypothyroidism may be the cause of hyponatremia. All hypothyroid patients with low serum sodium levels should be evaluated for other causes and superimposed factors of hyponatremia and treated accordingly.