Search

Backround: The effect of antihypertensive drugs on glucose homeostasis and insulin resistance remains an issue under investigation. There is evidence that renin-angiotensin system (RAS) blockers may favorably affect glucose metabolism, while treatment with calcium channel blockers (CCBs) is considered to have an overall neutral metabolic effect. However, the effects on glycemic indices may differ among agents within the same class of antihypertensive drugs. Objective: To evaluate the effects of different fixed-dose single pill combinations of RAS blockers with CCBs on homeostatic model assessment for insulin resistance (HOMA-IR). Methods:Drug-naive patients with arterial hypertension (AH) and impaired fasting glucose (IFG) were randomly allocated to open-label fixed, single pill combinations of valsartan 160 mg/day plus amlodipine 5 mg/day (VAL/AMLO group, n = 54), delapril 30 mg/day and manidipine 10 mg/day (DEL/MANI group, n = 53) or telmisartan 80 mg/day and amlodipine 5 mg/day (TEL/AMLO group, n = 51) for 12 weeks. Glycemic indices and HOMA-IR were determined at baseline and post-treatment. Results:A total of 158 patients were included. All treatment combinations effectively reduced blood pressure (systolic and diastolic) to similar levels (all p < 0.001). A decrease in the HOMA-IR index by 22.55% (p

Objective Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor. We present real-life characteristics of patients with increased Lp(a) levels attending a University Lipid Clinic. Methods We retrospectively studied patients attending the University of Ioannina Hospital Lipid Clinic with Lp(a) levels ≥30 mg/dL who were followed-up for a median of 22 months. Results One hundred eight patients (median age 59 years, 49% females) were included with median Lp(a) levels 67 mg/dL (30–320). Of patients, 25.1% had established atherosclerotic cardiovascular disease (ASCVD): 11.1 and 5.6% positive personal history of myocardial infarction (MI) and stroke, respectively, 6.5% carotid artery disease and 1.9% lower extremities arterial disease (LEAD). In addition, 35.2% of participants had heterozygous familial hypercholesterolemia (heFH), 37.9% positive family history of premature ASCVD, 29.6% hypertension, 12.0% diabetes and 5.5% chronic kidney disease (CKD). Of patients, 67.6% were receiving statin therapy and 16.6% additional ezetimibe at baseline visit, and 83 and 35% were receiving statin treatment and additional ezetimibe, respectively, during follow-up. Low-density cholesterol (LDL-C) levels and LDL-Ccorrected for Lp(a) levels were significantly reduced in lipid-lowering therapy naive patients by 37 and 40% (p 0.05), respectively, during follow-up. Lp(a) levels increased by 9% (p Conclusion Our data confirm the high prevalence of established ASCVD, hFH and positive familial history of premature ASCVD in patients with elevated Lp(a) levels. Lp(a) levels slightly increased during follow-up.

Background In randomized clinical trials, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein-cholesterol (LDL-C) with a favorable tolerability and safety profile. Our purpose is to provide real-world data regarding the indications, efficacy and safety of PCSK9i. Methods The cohort comprised 141 patients who attended the lipid clinic of 3 hospitals in Greece and started using PCSK9i. Patients were requested to attend the lipid clinic at 3 months and at 1 year. Results Ninety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). A PCSK9i [evolocumab 140 mg/2 weeks (n = 82), alirocumab 75 mg/2 weeks (n = 46) and alirocumab 150 mg/2 weeks (n = 13)] was prescribed due to failure to achieve LDL-C targets despite maximum lipid-lowering therapy (LLT) in 75% of patients, while in the remaining cases, the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2% and remained constant at 12 months (55.8% reduction from baseline). LDL-C target was achieved by 68.1% of patients at 3 months. “Totally” intolerant to statins patients (unable to tolerate any statin dose, n = 23) showed the lowest LDL-C reduction (47.7%). Side effects attributed to treatment were reported by 14 patients (10%). The total number of patients who stopped PCSK9i at 1 year was 14 (10%) but only 2 (1.4%) discontinued treatment because of side effects (myalgias). Conclusions Our real-world results of PCSK9i showed comparable efficacy and tolerability to those reported in clinical trials and highlighted the value of treatment with PCSK9i heFH patients not achieving LDL-C targets despite maximum LLT and high or very high risk statin intolerant patients.

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been demonstrated to be safe and effective in low-density lipoprotein cholesterol (LDL-C) lowering and cardiovascular risk reduction. Data on clinical implementation of PCSK9 inhibitors in real life setting in Greece is limited. Thus, we report 2-year experience with PCSK9 inhibitors in clinical practice at a University Hospital Lipid Clinic. Patients and methods: This is a retrospective study of patients who were first prescribed a PCSK9 inhibitor during 2016-2018. Patients had either established cardiovascular disease (CVD) and/or familial hypercholesterolemia (FH) and LDL-C level >100 mg/dL despite maximum tolerated high-intensity statin plus ezetimibe. Patient demographics, medical history, concomitant medications and laboratory results were documented during visits. Results: We included 37 patients (mean age 52 years, 56.8% males). Of patients, 28 (76%) had established CVD and 27 patients (74%) had FH. Concerning treatment, 33 patients (89%) were receiving high-intensity statin, while 35 patients (95%) were also on ezetimibe 10 mg. Addition of PCSK9 inhibitors (51% on evolocumab 140 mg per 2 weeks (Q2W), 22% on alirocumab 75 mg Q2W and 27% on alirocumab 150 mg Q2W) resulted in a reduction of total cholesterol by 42% and LDL-C by 59% after 2 months (p

A significant number of cardiovascular disease (CVD) patients, with the target lipid levels, as set by the guidelines, achieved, continue to remain at risk. In this setting, lipoprotein (Lp) a role in CVD prognosis is regaining interest. Although Lp(a) is related to the arteriosclerotic process, there is not currently an adequate amount of data for the inclusion of Lp(a) levels as a primary therapeutic target in the treatment of coronary artery disease (CAD) patients. In this framework, the current retrospective study aims to investigate the association of Lp(a) levels with the adverse cardiovascular (CV) events presented in a 10 year follow-up of CVD patients with dyslipidemia and its association with the major CV risk factors. A statistically significant reduction in Lp(a) levels was observed during the follow-up period (72.8±45.6 vs. 68.3±41.8 mg/dl; McNemar test; P0.001). The vast majority of patients who suffered a new acute myocardial infarction during the follow up period had Lp(a) levels30 mg/dl (24/28 patients, mean ± standard deviation Lp(a), 83.1±36.6 mg/dl, P=0.001). Kaplan-Meier survival analysis did not find statistically significant differences in a percutaneous coronary intervention (PCI) time occurrence during the follow-up period between patients with low (≤30 mg/dl) and high (30 mg/dl) Lp(a) levels (log-rank P=0.305). On the other hand, when a second and third PCI conducted during the monitoring period were included in the Kaplan Meier analysis as events, the mean time for a PCI was significantly shorter (7.2%; P=0.01) for patients with Lp(a) levels30 mg/dl. In conclusion, the current study reported that patients with high Lp(a) values are more prone to the occurrence of new myocardial infarction, while the Lp(a) cut-off value of 30 mg/dl was linked in CVD patients to an earlier need for PCI, especially in the most vulnerable group of patients with more than one (recurrent) revascularizations.

Objective: Olmesartan-induced enteropathy consists a syndrome that mimics celiac disease both clinically and histologically. Cases of this entity have sporadically been reported since 2012 and are usually characterized by severe diarrhea and malabsorption, followed by significant weight loss. Case Report: Herein, we report an uncommon case of this syndrome, where weight loss preceded several months the onset of gastrointestinal symptoms. Discussion and Conclusion: Physicians should be aware of unexplained weight loss in patients taking olmesartan, as prompt discontinuation of the drug may prevent the deleterious consequences of malabsorption.

Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61-0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82-1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43-0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.

Aim To investigate which metabolic factors increase the risk of incident diabetes (T2D) in statin-treated patients. Methods A retrospective study conducted in Greece including 1241 consecutive individuals with dyslipidemia attending a lipid clinic for ≥3 years. After defining associations with incident T2D, we assessed the risk of new-onset T2D based on the presence of impaired fasting glucose (IFG), atherogenic dyslipidemia, and overweight/obesity. Results After excluding 166 patients with baseline T2D and 193 subjects taking lipid-lowering therapy at the baseline visit, 882 participants were included in the study. Eleven percent ( n = 94) developed T2D during their follow-up (median 6 years; IQR: 4–10). Baseline patients’ age (OR: 1.05; 95% CI: 1.02–1.08, p p p p p p p = 0.01) and overweight/obesity (OR: 2.54; 95% CI: 1.14–5.66, p p Conclusion Atherogenic dyslipidemia appears to be an independent risk factor for new-onset T2D in statin-treated patients, while IFG, overweight/obesity and family history of diabetes remain risk factors for new-onset T2D in this group.

IntroductionThe main pathophysiologic mechanism of type 2 diabetes (T2D) is insulin resistance, which exists several years before T2D diagnosis. The term ‘prediabetes’ applies to patients with insulin resistance but without overt T2D. The improvement of glucose homeostasis in these patients may prevent or delay the development of T2D and its complications. Data suggest that fenugreek, olive leaf polyphenols and bergamot extract may improve carbohydrate metabolism. We examined the effect of an agent containing fenugreek, olive leaf polyphenols and bergamot extract (active agent) on glucose homeostasis in patients with prediabetes.Material and methodsThis was a single-center, randomized, double-blind, placebo-controlled trial; patients with prediabetes (N = 100) were randomized to treatment with the active agent or placebo. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) at 6 months after treatment initiation. Secondary endpoints included changes in other parameters of glucose metabolism and lipid profile.ResultsOverall 87 patients completed the study. No significant change in HbA1c was observed in either treatment group. Similarly, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid profile remained unaltered in both groups.ConclusionsThe administration of an agent containing fenugreek, olive leaf polyphenols and bergamot extract for 6 months did not improve glycemia or lipid parameters in patients with prediabetes.

Low-density lipoprotein cholesterol targets may not be achieved by statin monotherapy, especially in high-risk patients. Furthermore, in some patient subgroups, atherogenic dyslipidemia is observed. As a result, a combination of a statin with other hypolipidemic drugs may have additional benefits, especially in the form of a single tablet. The aim of this review is to present the novel fixed-dose drug combinations for the management of hyperlipidemia. Statins, ezetimibe, and fibrates have established their efficacy and safety in the treatment of hypercholesterolemia and hypertriglyceridemia. Clinical trials have shown that these hypolipidemic drug classes can be safely combined in order to augment the lipid-lowering efficacy. Furthermore, novel hypolipidemic drugs such as bembedoic acid and berberine have shown some promising initial results. The combination of different hypolipidemic regimens in a fixed-dose formulation can enhance the adherence to hypolipidemic treatment leading to improved outcomes. Moreover, complementary mechanisms of action of the combined hypolipidemic drugs may also provide additional benefits such as improvement in carbohydrate metabolism. As a result, fixed-dose combinations of hypolipidemic agents may provide an attractive option for the effective and safe management of hypercholesterolemia.

Summary Background Metabolic syndrome (MetS) patients can have low 25-hydroxyvitamin D 25(OH)VitD levels, which may be associated with increased oxidative stress. There is little data on the effect of 25(OH)VitD administration plus dietary intervention on oxidative stress markers in these patients. Aim To study the effect of 25(OH)VitD administration plus dietary intervention on oxidative stress markers in MetS patients. Methods This is a pre-specified analysis of a previously published study (NCT01237769 ClinicalTrials.gov). MetS participants (n = 50, 52 ± 10 years) were given dietary instructions and were randomized to 25(OH)VitD 2.000 IU/day p.o. (Suppl group) or no supplementation (No-Suppl group). Serum 25(OH)VitD, oxidized LDL (ox-LDL), paraoxonase activity (PON-1), arylesterase activity (ARYL) and urine 8-isoprostane (8-iso-PGF2a) levels were measured at baseline and after 3 months. Results MetS patients had low baseline 25(OH)VitD levels, which increased by 90% in the Suppl group [from 16.1 (3.3–35.1) to 30.6 (8.4–67.6) ng/mL, p = 0.001] and by 33.3% in the No-Suppl group [from 9.9 (4.0–39.6) to 13.2 (3.5–36.8) ng/mL, p = NS] after intervention. Ox-LDL, PON-1 and ARYL did not change significantly at follow-up in both groups, except for urine 8-iso-PGF2a levels that decreased by 22.7% in the Suppl group [from 48.8 (26.8–137.1) to 37.7 (12.3–99.0) ng/mmol creatinine, p = 0.015] and by 14.4% in No-Suppl group [from 45.8 (16.6–99.3) to 39.2 (13.3–120.1) ng/mmol creatinine, p = NS]. The reduction in 8-iso-PGF2a levels did not differ significantly between the 2 groups. Conclusion The administration of 25(OH)VitD plus dietary intervention in patients with MetS was not associated with meaningful reductions in oxidative stress markers compared with dietary intervention alone.

Background Metformin, in the absence of contraindications or intolerance, is recommended as first-line treatment for patients with type 2 diabetes mellitus (T2DM). This observational, retrospective study assessed the real-world adequacy of glycaemic control in Greek patients with T2DM initiating metformin monotherapy at maximum tolerated dose. Methods Included patients received metformin monotherapy for ≥24 months; relevant patient data were collected immediately prior to metformin initiation (baseline) and at other prespecified time points. The primary objective was to report, after 9 months of metformin treatment, the percentage of patients with baseline glycated haemoglobin (HbA1c) levels ≥6.5% (≥48 mmol/mol) achieving HbA1c Results Of the enrolled patients (N=316), 247 had baseline HbA1c ≥6.5%; following 9 months on metformin, 90 (36.4%) patients achieved HbA1c

Background: Familial Hypercholesterolaemia (FH) is the most common metabolic genetic disorder, with around 13 million people worldwide having the disease. However, FH is globally underdiagnosed and undertreated, while the vast majority of those treated do not achieve treatment goals. Objective: This review aims to clarify how to identify patients with FH. Methods: We performed a comprehensive search of the literature to identify available data. Results: Patients with FH are at high risk for cardiovascular events and death at an early age. Therefore, prompt detection of individuals with FH is of pivotal importance in order to implement appropriate preventive measures at a young age. Patient registries are a powerful tool for recording and monitoring a disease and encouraging clinical practices, subsequently improving outcomes and reducing healthcare costs. National FH registries are successfully applied in several countries (e.g. Spain, Denmark, UK, USA and the Netherlands). Importantly, in the last few years, the European Atherosclerosis Society (EAS) launched a global FH network aiming to collect data from specialized FH centres from different countries and establish a worldwide, standardised registry of patients with FH. Conclusion: It appears that the establishment and proper function of such registries will improve FH diagnosis, as well as preventive measures and management of FH patients.

Background: Hyponatremia is frequent in acute stroke patients, and it is associated with worse outcomes and increased mortality. Summary: Nonstroke-related causes of hyponatremia include patients’ comorbidities and concomitant medications, such as diabetes mellitus, chronic kidney disease, heart failure, and thiazides. During hospitalization, “inappropriate” administration of hypotonic solutions, poor solute intake, infections, and other drugs, such as mannitol, could also lower sodium levels in patients with acute stroke. On the other hand, secondary adrenal insufficiency due to pituitary ischemia or hemorrhage, syndrome of inappropriate antidiuretic hormone secretion, and cerebral salt wasting are additional stroke-related causes of hyponatremia. Although it is yet unclear whether the appropriate restoration of sodium level improves outcomes in patients with acute stroke, the restoration of the volume depletion remains the cornerstone of treatment in hypovolemic hyponatremia. In case of hyper- and euvolemic hyponatremia, apart from the correction of the underlying cause (e.g., withdrawal of an offending drug), fluid restriction, administration of hypertonic solution, loop diuretics, and vasopressin-receptor antagonists (vaptans) are among the therapeutic options. Key Messages: Hyponatremia is frequent in patients with acute stroke. The plethora of underlying etiologies warrants a careful differential diagnosis which should take into consideration comorbidities, concurrent medication, findings from the clinical examination, and laboratory measurements, which in turn will guide management decisions. However, it is yet unclear whether the appropriate restoration of sodium level improves outcomes in patients with acute stroke.

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases. Findings Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53.6%] women) from 56 countries were included in the study. Of these, 31 798 (75.4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84.2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46.2 years (IQR 34.3-58.0); median age at diagnosis of familial hypercholesterolaemia was 44.4 years (32.5-56.5), with 40.2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17.4% (2.1% for stroke and 5.2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81.1%) were receiving statins and 3691 (21.2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5.43 mmol/L (IQR 4.32-6.72) among patients not taking lipid-lowering medications and 4.23 mmol/L (3.20-5.66) among those taking them. Among patients taking lipid-lowering medications, 2.7% had LDL cholesterol lower than 1.8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1.8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p, Pfizer Independent Grant for Learning Change [16157823]; Amgen; Merck Sharp Dohme; Sanofi-Aventis; Daiichi Sankyo; Regeneron; National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK; NIHR; Czech Ministry of Health [NU20-02-00261]; Canadian Institutes of Health Research; Austrian Heart Foundation; Tyrolean Regional Government; Gulf Heart Association, The EAS FHSC is an academic initiative that has received funding from a Pfizer Independent Grant for Learning & Change 2014 (16157823) and from investigator-initiated research grants to the European Atherosclerosis Society-Imperial College London from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron. KKR acknowledges support from the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre, UK. KID acknowledges support from a PhD Studentship from NIHR under the Applied Health Research programme for Northwest London, UK (the views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health). TF was supported by a grant from the Czech Ministry of Health (NU20-02-00261). JG receives support from the Canadian Institutes of Health Research. The Austrian Familial Hypercholesterolaemia registry has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Gulf Familial Hypercholesterolaemia registry was done under the auspices of the Gulf Heart Association.

IntroductionObesity is associated with cardiovascular disease (CVD) risk factors as well as decreased 25(OH) vitamin D serum levels. We aimed to study 25(OH) vitamin D levels in adolescents with obesity compared with normal weight controls in association with CVD risk factors, and the possible effect of vitamin D supplementation.Material and methodsIn a cross-sectional study, 69 obese and 34 normal-weight adolescents were included. In an interventional study 15 adolescents with obesity and vitamin D insufficiency were given 2000 IU vitamin D per os daily for 3 months.ResultsAdolescents with obesity had significantly lower 25(OH) vitamin D levels compared with normal-weight controls (12.0 (3.0–36.0) vs. 34.0 (10.0–69.0) ng/ml, respectively, p < 0.001). In adolescents with obesity, 25(OH) vitamin D was inversely associated with leptin even after adjustment for body mass index (BMI) (r = –0.340, p = 0.009). Conversely, 25(OH) vitamin D was not related with other parameters, such as BMI, blood pressure, lipids, glucose, insulin, homeostasis model assessment (HOMA) index, adiponectin, leptin/adiponectin ratio, and visfatin levels. Following supplementation in 15 vitamin D insufficient adolescents with obesity, 25(OH) vitamin D significantly increased (from 17.3 (12.5–27.8) to 32.6 (14.3–68.0) ng/ml, p = 0.005) and so did low-density lipoprotein cholesterol (LDL-C) (from 85.4 ±9.5 to 92.1 ±15.8 mg/dl, p = 0.022), while there were reductions in glycated haemoglobin (HbA1c) (from 5.8 ±0.2 to 5.5 ±0.1%, p = 0.03) and leptin (from 19.7 (7.8–45.5) to 15.1 (4.3–37.3) ng/ml, p = 0.03). Oxidised LDL, paraoxonase, arylesterase, and urine isoprostanes remained unchanged.ConclusionsAdolescents with obesity had lower 25(OH) vitamin D, which may be associated with higher leptin levels. Vitamin D supplementation may lead to HbA1c and leptin reductions, but also to an increase in LDL-C.

In clinical practice, several medications such as diuretics, psychotropic drugs, and anticonvulsants have been reported to be a frequent cause of hyponatremia. Drugs may cause hyponatremia either by affecting the homeostasis of sodium and water (e.g., diuretics) or by altering the water homeostasis as a consequence of the syndrome of inappropriate secretion of antidiuretic hormone. On the contrary, drugs commonly prescribed in everyday clinical practice, including proton pump inhibitors, antibiotics, angiotensin-converting enzyme inhibitors, hypoglycemic agents and, amiodarone, have been infrequently 'incriminated' as causes of hyponatremia. Therefore, in the diagnostic approach of patients with low serum [Na+] levels, meticulous history taking and recording of pharmacotherapy is warranted to identify potentially culprit medications. Taking into account the adverse outcomes associated with even mild hyponatremia (i.e., impaired cognition, falls and fractures, mortality), recognition of drug-induced hyponatremia is of vital importance, while responsible agents should be discontinued and "re-challenge" should be avoided by informing the patient and involved caregivers.

Introduction Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. Furthermore, it is associated with increased morbidity and mortality. Areas covered This review discusses the efficacy and side effects of the currently available treatment options for hyponatremia and the differences in the pharmacological approach between the European and USA guidelines. Additionally, the authors provide their expert perspectives on current treatment strategies and what they expect from this field in the future. Expert opinion Several pharmacological options are available for the treatment of hyponatremia, but data from trials examining and comparing these treatments are missing. Regarding chronic hyponatremia, the role of vaptans should be further analyzed, focusing on comparisons with other active treatments on patient-relevant outcomes and not only on serum sodium concentration. Clinicians should be cautious to an overly rapid increase in serum sodium levels with all available treatment strategies. Finally, it is important to ascertain whether correction of serum sodium levels improves mortality in hyponatremic patients.

Obesity is a key factor for cardiovascular diseases and complications. Obesity is associated with hypertension, dyslipidemia and type II diabetes, which are the major predictors of cardiovascular disease in the future. It predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke that are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.Epidemiology and mechanisms of obesity-induced hypertension, diabetes and dyslipidemia will be reviewed and the role of lifestyle modification and treatment strategies in obesity will be updated and analyzed. The best treatment options for people with obesity, hypertension, diabetes and dyslipidemia will discussed.

Introduction Current European guidelines recommend treatment with lipid-lowering therapy (LLT) to a low-density lipoprotein cholesterol (LDL-C) target of < 70 mg/dl for patients at very high risk. LDL-C target attainment and use of LLTs in these patients in Greece is not known. Material and methods The Dyslipidemia International Study (DYSIS) II was a multicenter observational study. The coronary heart disease (CHD) cohort was divided into two groups based on treatment status (on LLT for ≥ 3 months or not on LLT). The acute coronary syndrome (ACS) cohort was evaluated at the time of admission and again 120 ±15 days after admission. Results In the CHD cohort (n = 499), 457 (91.6%) patients were on LLT. The LDL-C target value was attained by 26.5% of LLT users. Statin monotherapy was used by 77.5% of treated patients, with a mean ± SD atorvastatin dose equivalent of 24 ±16 mg/day. In the ACS cohort (n = 200), 159 (79.5%) patients were on LLT at admission. Mean ± SD LDL-C levels were 108 ±40 mg/dl at admission and 86 ±25 mg/dl at follow-up. LDL-C target value attainment rates were 16.2% at admission and 25.0% at follow-up. At admission, statin monotherapy was used by 86.8% of treated patients. The mean ± SD atorvastatin dose equivalent increased from 20 ±14 mg/day at admission to 29 ±15 mg/day at follow-up. The statin dose was associated with higher odds of LDL-C target value attainment (OR = 1.05, 95% CI: 1.02–1.08). Conclusions The LDL-C target attainment by very high risk patients in Greece is suboptimal. Increasing the statin dose or combining it with non-statins may improve target value attainment.

Objective Nephropathy is among the most common and most devastating complications of diabetes mellitus. Recent data suggest that there is a multifaceted interaction between the kidney and antidiabetic drugs. Thus, the deterioration of renal function may result in important changes in the pharmacokinetic and pharmacodynamic properties of glucose-lowering compounds. Additionally, drugs that exert their antidiabetic properties through the inhibition of proximal glucose reabsorption are now available whereas accumulating evidence suggests that some of these drugs may exert renoprotective properties that are independent of their effect on carbohydrate metabolism. Methods All articles published until the end of 2016 in PubMed that dealt with the relationship of antidiabetic drugs and the kidney were reviewed and the relevant information is presented here. Results In this review, we summarize the available evidence on the drugs that act through the inhibition of renal glucose reabsorption, discuss the adjustments in the dose of antidiabetic drugs in patients with various stages of kidney disease and explore the renoprotective potency of the various glucose-lowering compounds. Conclusion Sodium glucose cotransporter 2 inhibitors represent a very promising option for the treatment of type 2 diabetes, especially in patients with established cardiovascular disease. These drugs, along with pioglitazone and incretin mimetics may also reduce the incidence and the rate of progression of diabetic nephropathy.

Glucagon like peptide-1 receptor agonists and dipeptidyl peptidase-IV inhibitors (collectively termed incretin-based therapies) represent two of the most widely used classes of antidiabetic drugs. These compounds exert their beneficial effects on carbohydrate metabolism through the activation of specific glucagon like peptide-1 receptors in various organs. Accumulating evidence suggests that glucagon like peptide-1 receptor agonists and dipeptidyl peptidase-IV inhibitors also affect renal function in both glucagon like peptide-1 receptor-dependent and independent manner. However, the clinical significance of these observations remains indeterminate. In this review, we summarize the available preclinical and clinical data on the effects of incretin-based therapies on renal function indices and discuss their relevance in everyday clinical practise.

Objective: Mesenteric panniculitis (MP) and sclerosing mesenteritis is an umbrella term used to describe a rare, chronic, and frequently benign fibrosing inflammatory disease that affects the adipose tissue of the mesentery. The diagnosis is usually based on imaging (computed tomography &lsqb;CT] or magnetic resonance imaging) findings and is confirmed by biopsy. We report the unusual case of a patient with MP with typical CT findings and diabetes mellitus (DM).Methods: A 48-year-old male presented for symptomatic new onset DM. An abdominal CT scan revealed a well-defined mesenteric mass compatible with MP. The combination of insulin degludec and sitagliptin/metformin resulted in a decrease of HbA1c; however, this was followed by a subsequent gradual increase in HbA1c and positive glutamic acid decarboxylase auto-antibodies.Results: The patient developed auto-immune DM that was confirmed by the presence of auto-antibodies.Conclusion: Panniculitis has been infrequently reported in patients with type 2 DM. This is the first report of a patient with MP correlated with auto-immune DM. The possible pathophysiologic mechanisms are discussed.Abbreviations: CT computed tomography DM diabetes mellitus HbA1c hemoglobin A1c MP mesenteric panniculitis SM sclerosing mesenteritis

The direct oral anticoagulant rivaroxaban is useful in various indications that include venous deep vein thrombosis prophylaxis/treatment after knee/hip replacement surgery and prevention of stroke in patients with non-valvular atrial fibrillation. Its mechanism of action has been mostly associated with hemorrhage-related adverse effects; thus a number of non-hemorrhage-related adverse effects of the drug have received less attention or go unrecognized. These adverse effects mainly include liver injury, hypersensitivity reactions, leukocytoclastic vasculitis and hair loss. Clinicians should be aware of these rare adverse reactions and advise their patients to contact them as soon as they observe any unexpected clinical response.

Decreased serum sodium concentration is a rather frequent electrolyte disorder in the elderly population because of the presence of factors contributing to increased antidiuretic hormone, the frequent prescription of drugs associated with hyponatremia and also because of other mechanisms such as the “tea and toast” syndrome. The aim of this review is to present certain challenges in the evaluation and treatment of hyponatremia in the elderly population and provide practical solutions. Hyponatremia in elderly subjects is mainly caused by drugs (more frequently thiazides and antidepressants), the syndrome of inappropriate antidiuretic hormone secretion (SIAD) or endocrinopathies; however, hyponatremia is multifactorial in a significant proportion of patients. Special attention is needed in the elderly population to exclude endocrinopathies as a cause of hyponatremia before establishing the diagnosis of SIAD, which then requires a stepped diagnostic approach to reveal its underlying cause. The treatment of hyponatremia depends on the type of hyponatremia. Special attention is also needed to correct serum sodium levels at the appropriate rate, especially in chronic hyponatremia, in order to avoid the osmotic demyelination syndrome. In conclusion, both the evaluation and the treatment of hyponatremia pose many challenges in the elderly population.

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with low-density lipoprotein (LDL) catabolism, but its serum concentration is not uniformly associated with cardiovascular disease in clinical studies. Obesity is linked with increased cardiovascular risk, but the effect of increased body weight and short-term weight loss on serum PCSK9 levels is not well studied. Material and methods: The aim of this prospective pilot study was to assess differences in serum PCSK9 levels (determined with a quantitative sandwich enzyme immunoassay) between otherwise healthy drug-naïve obese subjects and healthy individuals with normal body weight. Additionally, PCSK9 levels were determined at baseline and after a 3-month weight-loss program with a low-fat diet in a randomly assigned subgroup of the obese subjects (n = 15). Results: Obese subjects (n = 35) were older (age: 43 ± 11 years) and had significantly higher body mass index, total cholesterol, triglycerides, LDL cholesterol (LDL-C), apolipoprotein B and homeostasis model assessment of insulin resistance (HOMA) index levels, as well as significantly lower high-density lipoprotein cholesterol (HDL-C) concentration, compared with normal-weight subjects (n = 20, age: 35 ± 6 years). Serum PCSK9 levels were significantly higher in obese subjects compared with normal-weight individuals, even after adjustment for age, LDL-C, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, apolipoprotein E, glucose, insulin and HOMA index levels (p = 0.018). Obese subjects experienced significant weight loss (from 109 ± 22 to 104 ± 23 kg, p < 0.01), but serum PCSK9 levels did not significantly change after the 3-month weight-loss program. Conclusions: Serum PCSK9 levels are higher in obese subjects than in normal-weight individuals. Short-term weight loss with a low-fat diet does not significantly affect PCSK9 levels.

Introduction: Patients with metabolic syndrome (MetS) may have lower 25-hydroxyvitamin D (25(OH)VitD) serum levels compared with non-MetS individuals. Vitamin D (VitD) deficiency is associated with various cardiovascular disease (CVD) risk factors. Yet, the effect of VitD supplementation on MetS remains uncertain. Our aim was to examine the effect of VitD supplementation on CVD risk factors in MetS subjects. Material and methods: This pilot study had a PROBE (prospective, randomised, open-label, blinded end-point) design. Fifty patients with MetS were included and randomised either to dietary instructions (n = 25) (control group) or dietary instructions plus VitD 2000 IU/day (n = 25) (VitD group) for 3 months. This study is registered in ClinicalTrials.gov (NCT01237769). Results: In both groups a similar small weight reduction was achieved. In the VitD group serum 25(OH)VitD levels significantly increased by 91% (from 16.0 (3.0–35.0) to 30.6 (8.4–67.0) ng/ml, p < 0.001), while in the control group no significant change was observed (from 10.0 (4.0–39.6) to 13.0 (3.5–37.0) ng/ml). In both groups triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, haemoglobin A1c, homeostasis model assessment index and diastolic blood pressure did not significantly change. Systolic blood pressure decreased by 3.7% (from 134 ±14 to 129 ±13 mm Hg, p = 0.05) in the VitD group, while it decreased by 1.5% (from 132 ±13 to 130 ±16 mm Hg, p = NS) in the control group (p = NS between groups). In the VitD group serum 25(OH)VitD increase was negatively correlated with SBP decrease (r = –0.398, p = 0.049). Conclusions: VitD supplementation (2000 IU/day) did not affect various CVD risk factors in patients with MetS.

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60 mL/min/1.73 m2. The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: 6 mg/dL.Results: After excluding patients with baseline eGFR

Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor, but other lipid variables such as triglycerides (TRGs), high-density lipoprotein cholesterol (HDL-C) and lipoprotein a [Lp(a)] also affect cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-C concentration but also modestly improve the concentrations of TRGs and HDL-C and more robustly decrease Lp(a) levels. The review presents the associated mechanisms of the beneficial effects of PCSK9 inhibitors on the other than LDL-C lipid variables, including the effects on lipid/apolipoprotein secretion and clearance and the heteroexchange between lipoproteins, as well as the possible effects on other variables involved in lipid metabolism such as sortilin. Proprotein convertase subtilisin/kexin type 9 inhibitors improve the overall lipid profile, and these beneficial effects may play a role in the reduction of cardiovascular risk.

The use of antidiabetic drugs is expected to substantially increase since diabetes mellitus incidence rises. Currently used antidiabetic drugs have a positive safety profile, but they are associated with certain acid-base and electrolyte abnormalities. The aim of the review is to present the current data regarding the antidiabetic drugs-associated acid-base and electrolyte abnormalities. Areas covered: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been linked with the scarce, but serious, complication of euglycemic diabetic ketoacidosis, as well as with an increase in serum potassium, magnesium and phosphorus levels. Metformin use has been associated with the development of lactic acidosis, although many studies have doubt the direct link with this serious complication. Additionally, metformin in some studies has been linked with a decrease in serum magnesium levels. Insulin administration is associated with a reduction in serum potassium, magnesium and phosphorus concentration, along with reduced renal magnesium excretion. Pioglitazone is associated with an increase in serum magnesium levels. Current data regarding the pathophysiological mechanisms, precipitants, risk factors and presentation of the above abnormalities are discussed in the present review. Expert opinion: Clinicians should choose appropriately between antidiabetic drugs based not only on their hypoglycemic efficacy and effects on cardiovascular risk but also based on the patient's specific risk to develop acid-base or electrolyte derangements.

Aim To investigate the value of CHADS 2 and CHA 2 DS 2 -VASc scores in predicting atrial fibrillation (AF) among dyslipidemic individuals and assess the additional value of incorporating low levels of high-density lipoprotein cholesterol (HDL-C). Methods This observational study included 1241 individuals attending a lipid clinic. Models including clinical and laboratory parameters were constructed to test the predictive value of CHADS 2 and CHA 2 DS 2 -VASc scores as well as low HDL-C levels for incident AF. Low HDL-C levels were defined as Results After excluding 18 patients with AF at baseline, 1223 subjects were followed-up for a median period of 6years (IQR: 4–10), and 34 (2.8%) developed AF. Baseline CHADS 2 (OR: 1.71; 95% CI: 1.28–2.29, p 2 DS 2 -VASc scores (OR: 1.56; 95% CI: 1.26–1.92, p p 2 and CHA 2 DS 2 -VASc scores were significant predictors for new-onset AF (C-Statistic: CHADS 2 0.679, p 2 DS 2 -VASc 0.698, p 2 scores were associated with reduced event-free survival from AF (log-rank=10.62, p =0.001) with differences potentiated if stratified by CHA 2 DS 2 -VASc score (log-rank=22.29, p p Conclusions CHADS 2 and CHA 2 DS 2 -VASc scores predict new AF in dyslipidemic patients. Risk prediction improved modestly when low HDL-C levels were included.

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.

Sitosterolemia is a metabolic disorder characterized by increased intestinal absorption and tissue accumulation of phytosterols. Although sitosterolemia is considered a rare disease, its prevalence may be significantly higher than initially thought. Indeed, accumulating evidence suggests that patients with unexplained hematologic abnormalities or premature cardiovascular disease in the absence of classic risk factors may exhibit disordered phytosterol metabolism. In this review, we present a patient with sitosterolemia, describe the pathophysiology and the clinical picture of this disorder, and discuss the clinical value of phytosterol supplementation in patients with primary dyslipidemias.

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.

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.

Background Patients with moderate to severe hypothyroidism and mainly patients with myxedema may exhibit reduced sodium levels ( 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.