Long-term risk, clinical management, and healthcare resource utilization of stable patients with coronary artery disease and post-myocardial infarction in Greece - TIGREECE study.

BACKGROUND: In light of the scarcity of evidence, TIGREECE evaluated the clinical management and long-term outcomes of patients at high risk for an atherothrombotic event who have suffered a myocardial infarction (MI), managed by cardiologists/internists in routine hospital and private office settings in Greece. METHODS: TIGREECE, a multicenter, 3-year prospective cohort study, enrolled patients ≥50 years old, with a history of MI 1-3 years before enrollment and with at least one of the following risk factors: age ≥65 years, diabetes mellitus requiring medication, second prior MI, multivessel coronary artery disease, and creatinine clearance 15-60 mL/min. The primary outcome was a composite of MI, unstable angina with urgent revascularization, stroke, or all-cause death. RESULTS: Between 5 June 2014 and 25 July 2015, 305 eligible consented patients (median age: 67.3 years; 81.3% males; 14.8% active smokers; 80.7% overweight/obese) were enrolled; 52.5% had ≥2 qualifying risk factors. The median time from the index MI [ST-segment elevation myocardial infarction (STEMI) in 51.1%, non-STEMI in 33.1%] to enrollment was 1.7 years. Of the patients, 65.9% had been discharged on dual antiplatelet therapy. At enrollment, 94.4% were receiving antiplatelets: 60.0% single [acetylsalicylic acid (ASA): 43.3%; clopidogrel: 15.7%] and 34.4% dual (ASA + clopidogrel: 31.8%) therapy. The Kaplan-Meier estimated 3-year primary composite event rate was 9.3% [95% confidence interval (CI): 6.4-13.0), and the ischemic composite event rate was 6.7% (95% CI: 4.2-9.9). CONCLUSIONS: Study results indicate that in the routine care of Greece one in ten patients experience a recurring cardiovascular event or death, mainly of ischemic origin, 1-3 years post-MI.

The Effect of Commonly Used Fixed-Dose Single Pill Combinations of Renin-Angiotensin-System Blockers and Calcium Channel Blockers on HOMA-IR Index in Hypertensive Patients with Impaired Fasting Glucose: a 12-Week Randomized Open-Label Prospective Study.

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 <0.01) was noted following treatment with TEL/AMLO, while an increase by 1.4% (p = 0.57) and 12.65% (p = 0.072) was observed in the VAL/AMLO group and the DEL/MANI group, respectively. These changes were significantly different between TEL/AMLO and DEL/MANI (p < 0.05) as well as between TEL/AMLO and VAL/AMLO (p < 0.001). Conclusion:Despite similar antihypertensive action, the effect of fixed, single pill combinations with TEL/AMLO, VAL/AMLO and DEL/MANI on insulin resistance is in favor of TEL/AMLO. Trial registration: The study protocol was published online in https://diavgeia.gov.gr/ (No: ÂÈ6Ó46906Ç-ÁÅÓ) via the Ministry of Digital Governance, after receiving approval from the Scientific Council and Administrative Council of University Hospital of Ioannina (No. of approval: 1/12-06-2014 (issue 150). https://diavgeia.gov.gr/decision/view/%CE%92%CE%986%CE%A346906%CE%97- %CE%91%CE%95%CE%A3 h t t p s : / / d i a v g e i a . g o v . g r / d o c / % C E % 9 2 % C E % 9 8 6 % C E % A 3 4 6 9 0 6 % C E % 9 7 - %CE%91%CE%95%CE%A3?inline=true.

Moderately elevated lipoprotein (a) levels are associated with an earlier need for percutaneous coronary intervention in recurrent cardiovascular disease.

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; P<0.001). The vast majority of patients who suffered a new acute myocardial infarction during the follow up period had Lp(a) levels >30 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) levels >30 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.

Lipoprotein(a): A Concealed Precursor of Increased Cardiovascular Risk? A Real-World Regional Lipid Clinic Experience.

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), in lipid-lowering therapy intensified patients by 31 and 36% (p <0.05), and in patients on stable lipid-lowering treatment by 15% (p <0.05) and 10% (p >0.05), respectively, during follow-up. Lp(a) levels increased by 9% (p <0.05). 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.

Recommendations for lipid modification in patients with ischemic stroke or transient ischemic attack: A clinical guide by the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society.

This document presents the consensus recommendations of the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society for lipid modification in patients with ischemic stroke or transient ischemic attack. This clinical guide summarizes the current literature on lipid management and can be of assistance to the physicians treating stroke patients in clinical practice.

Early Signs of Atherogenic Features in the HDL Lipidomes of Normolipidemic Patients Newly Diagnosed with Type 2 Diabetes.

Cardiovascular disease (CVD) is the major cause of death in patients with type-2 diabetes mellitus (T2DM), although the factors that accelerate atherosclerosis in these patients are poorly understood. The identification of the altered quantity and quality of lipoproteins, closely related to atherogenesis, is limited in routine to a pattern of high triglycerides and low HDL-cholesterol (HDL-C) and in research as dysfunctional HDLs. We used the emerging NMR-based lipidomic technology to investigate compositional features of the HDLs of healthy individuals with normal coronary arteries, drug-naïve; recently diagnosed T2DM patients with normal coronary arteries; and patients with recent acute coronary syndrome. Patients with T2DM and normal serum lipid profiles even at diagnosis presented significant lipid alterations in HDL, characterized by higher triglycerides, lysophosphatidylcholine and saturated fatty acids; and lower cholesterol, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, plasmalogens and polyunsaturated fatty acids, an atherogenic pattern that may be involved in the pathogenesis of atherosclerosis. These changes are qualitatively similar to those found, more profoundly, in normolipidemic patients with established Coronary Heart Disease (CHD). We also conclude that NMR-based lipidomics offer a novel holistic exploratory approach for identifying and quantifying lipid species in biological matrixes in physiological processes and disease states or in disease biomarker discovery.

Adherence to the National Guidelines for Follow-Up Protocol in Subjects with Type 2 Diabetes Mellitus in Greece: The GLANCE Study.

INTRODUCTION: Physician adherence, or lack therefore, to diabetes care and follow-up guidelines may be linked to the rates of achieving suboptimal glycaemic, blood pressure and lipid targets in people with type 2 diabetes mellitus (T2DM). In this cross-sectional study we evaluated physician adherence to the patient follow-up protocol (PFP) of the 2017 Hellenic Diabetes Association (HDA) guidelines and also assessed glycated haemoglobin (HbA1c), blood pressure and lipid control achievement rates in the routine care setting in Greece. METHODS: Eligible subjects were adults with T2DM receiving oral hypoglycaemic agents (OHAs) for ≥ 1 year who had ≥ 2 HbA1c measurements in the previous year and an HbA1c target < 7%. Overall adherence at the subject level was defined as the percentage of the 62 HDA PFP items that had been met during the past year. RESULTS: Between June and December 2018, 601 eligible subjects (54.6% men; mean age 65.2 years; median T2DM duration 5.9 years, of whom 96.5% had ≥ 1 medical condition/comorbidity), were enrolled into the study by 53 hospital- and office-based endocrinologists, internists and general practitioners. The main OHAs prescribed at enrolment were metformin (91.0%), dipeptidyl peptidase-4 inhibitors (60.7%), sodium-glucose co-transporter-2 inhibitors (23.5%) and sulphonylureas (16.3%). Mean overall physician adherence to the PFP was 43.6%. Predictors of greater higher physicans' adherence were female sex (p = 0.026), > 3 medical conditions/comorbidities (p = 0.043) and diabetic complications (p < 0.001). HbA1c, low-density lipoprotein-cholesterol, systolic/diastolic blood pressure and composite metabolic targets were achieved by 82.1, 57.0, 42.6 and 21.6% of subjects, respectively. CONCLUSIONS: In Greek routine care, physician adherence to the PFP of the 2017 HDA guidelines is suboptimal. Future efforts should focus on identifying the barriers to an adequate adherence by physicians to the full PFP, with the aim to provide optimal patient care.

Vitamin D status and cardiometabolic risk factors in Greek adolescents with obesity - the effect of vitamin D supplementation: a pilot study.

INTRODUCTION: Obesity 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 METHODS: In 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. RESULTS: Adolescents 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. CONCLUSIONS: Adolescents 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.

Cardioprotective Properties of HDL: Structural and Functional Considerations.

BACKGROUND: As Mendelian Randomization (MR) studies showed no effect of variants altering HDL-cholesterol (HDL-C) levels concerning Cardiovascular Disease (CVD) and novel therapeutic interventions aiming to raise HDL-C resulted to futility, the usefulness of HDL-C is unclear. OBJECTIVE: As the role of HDL-C is currently doubtful, it is suggested that the atheroprotective functions of HDLs can be attributed to the number of HDL particles, and their characteristics including their lipid and protein components. Scientific interest has focused on HDL function and on the causes of rendering HDL particles dysfunctional, whereas the relevance of HDL subclasses with CVD remains controversial. METHODS: The present review discusses changes in quality as much as in quantity of HDL in pathological conditions and the connection between HDL particle concentration and cardiovascular disease and mortality. Emphasis is given to the recently available data concerning the cholesterol efflux capacity and the parameters that determine HDL functionality, as well as to recent investigations concerning the associations of HDL subclasses with cardiovascular mortality. RESULTS: MR studies or pharmacological interventions targeting HDL-C are not in favor of the hypothesis of HDL-C levels and the relationship with CVD. The search of biomarkers that relate with HDL functionality is needed. Similarly, HDL particle size and number exhibit controversial data in the context of CVD and further studies are needed. CONCLUSION: There is no room for the old concept of HDL as a silver bullet,as HDL-C cannot be considered a robust marker and does not reflect the importance of HDL particle size and number. Elucidation of the complex HDL system, as well as the finding of biomarkers, will allow the development of any HDL-targeted therapy.

Real-World Adequacy of Glycaemic Control in Treatment-Naïve Greek Patients with Type 2 Diabetes Mellitus Initiating Treatment with Metformin Monotherapy at the Maximum Tolerated Dose: The Reload Study.

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<6.5%. Secondary objectives included the assessment of time spent with poor glycaemic control and time to treatment intensification. A sensitivity analysis assessed the percentage of patients with baseline HbA1c≥7% (≥53 mmol/mol) achieving HbA1c<7% (<53 mmol/mol). RESULTS: Of the enrolled patients (N=316), 247 had baseline HbA1c ≥6.5%; following 9 months on metformin, 90 (36.4%) patients achieved HbA1c<6.5% (mean HbA1c change-1.3% [-14 mmol/mol]). Median time of exposure to HbA1c ≥6.5% was 23.4 months and time to treatment intensification was 28.0 months. The sensitivity analysis revealed that the proportion of patients achieving HbA1c<7.0% was 50% (mean HbA1cpy for up to 24 months. Addressing clinical inertia could improve disease outcomes and, possibly, economic burden.

Arterial Stiffness, Cognitive Dysfunction and Adherence to Antihypertensive Agents. Is there a Link to Hypertensive Patients?

The incidence of hypertension (HTN) and its cardiovascular (CV) complications are increasing throughout the world. Blood pressure (BP) control remains unsatisfactory worldwide. Medical inertia and poor adherence to treatment are among the factors that can partially explain, why BP control rate remains low. The introduction of a method for measuring the degree of adherence to a given medication is now a prerequisite. Complex treatment regimes, inadequate tolerance and frequent replacements of pharmaceutical formulations are the most common causes of poor adherence. In contrast, the use of stable combinations of antihypertensive drugs leads to improved patient adherence. We aim to review the relationships between arterial stiffness, cognitive function and adherence to medication in patients with HTN. Large artery stiffening can lead to HTN. In turn, arterial stiffness induced by HTN is associated with an increased CV and stroke risk. In addition, HTN can induce disorders of brain microcirculation resulting in cognitive dysfunction. Interestingly, memory cognitive dysfunction leads to a reduced adherence to drug treatment. Compliance with antihypertensive treatment improves BP control and arterial stiffness indices. Early treatment of arterial stiffness is strongly recommended for enhanced cognitive function and increased adherence.

Drug-Induced Hypophosphatemia: Current Insights.

Phosphate is actively involved in many important biochemical pathways, such as energy and nucleic acid metabolism, cellular signaling, and bone formation. Hypophosphatemia, defined as serum phosphate levels below 2.5 mg/dL (0.81 mmol/L), is frequently observed in the course of treatment with commonly used drugs, such as diuretics, bisphosphonates, antibiotics, insulin, and antacids. Furthermore, this undesired effect may complicate the use of several novel medications, including teriparatide, denosumab, parenteral iron, and antiviral and antineoplastic agents. This review addresses drug-associated hypophosphatemia, focusing on underlying mechanisms and the most recent knowledge on this topic, in order to increase the insight of clinicians, with reference to early diagnosis and appropriate management.

PCSK9 inhibitors in clinical practice: Novel directions and new experiences.

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.

Hyponatremia in Acute Stroke Patients: Pathophysiology, Clinical Significance, and Management Options.

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.

Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes.

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.

No effect of fenugreek, bergamot and olive leaf extract on glucose homeostasis in patients with prediabetes: a randomized double-blind placebo-controlled study.

INTRODUCTION: The 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 METHODS: This 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. RESULTS: Overall 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. CONCLUSIONS: The 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.

Attainment of cholesterol target values in Greece: results from the Dyslipidemia International Study II.

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.

Influence of Supervised Disease Understanding and Diabetes Self-Management on Adherence to Oral Glucose-Lowering Treatment in Patients with Type 2 Diabetes.

INTRODUCTION: Systematic patient education has been reported to improve adherence to treatment, leading to better clinical outcomes. This cluster randomized real-world study investigated the effect of a systematic education program and telephone support on self-reported adherence to oral glucose-lowering treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: Centers were randomized (1:1) to provide either standard-of-care (control group) or standard-of-care along with the education program and telephone support (empowerment group). Adherence to treatment and satisfaction with treatment were assessed using the four-item Morisky Medication Adherence Scale (MMAS-4) and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). The study population included 457 patients (258/199 male/female) with T2DM and non-optimal glycemic control, on oral antidiabetic treatment (age 62.7 [11.4]; disease duration 8.5 [6.5] years). RESULTS: MMAS-4 high adherence rates for the control and empowerment groups were increased by 3.8% and 16.8% at 4 months (Breslow-Day test p = 0.04) and by 8.5% and 18.8% at 8 months of follow-up, respectively (Breslow-Day test p = 0.09), compared to baseline. Intense physical activity was increased in both control and empowerment groups by 2.3% and 13.9% at 4 months (Breslow-Day test p = 0.082) and by 4.0% and 22.5% at 8 months of follow-up (Breslow-Day test p < 0.001). Baseline mean (SD) HbA1c was significantly lower in the control group compared with the empowerment group [7.7% versus 8.0%, p = 0.001] and decreased in both groups at 4 months by 0.7% and 0.9%, respectively. The change from baseline in the mean DTSQ status score at 4 months was greater in the empowerment group, and the effect was sustained at 8 months (control group: 29.1, 30.5, and 30.9; empowerment group: 25.0, 28.7, and 29.4 at baseline, 4 and 8 months, respectively, p < 0.001). CONCLUSION: Systematic education combined with telephone support delivered by physicians might be associated with improvement in treatment adherence and treatment satisfaction in patients with T2DM. FUNDING: MSD, Greece.