Non-Classical Aspects of Obesity Pathogenesis and Their Relative Clinical Importance for Obesity Treatment.

Obesity is a chronic disease and a major public health problem due to its association with non-communicable diseases and all-cause mortality. An increased energy intake and decreased physical activity have been long recognized as the classical parameters that contribute to the development of obesity. However, several other, non-classical factors have also been associated with obesity through various complex mechanisms. Some of them are diet related, such as diet quality, dietary habits and speed of eating. Other factors are non-dietary, such as endocrine-disrupting chemicals, sleep quality and quantity, psychotropic medications and light at night. The scope of the present narrative review is to address these non-classical factors that are implicated in the pathogenesis of obesity, to clarify their potential role in the management of obesity and, where possible, to provide some practical clinical recommendations.

Weight Loss Versus Glycemic Control as the Primary Treatment Target in Newly Diagnosed Type 2 Diabetes: Why Choose When You Can Have Both?

Weight loss has been associated with significant improvements in glycemic control, quality of life, and comorbidities in people with type 2 diabetes. Furthermore, achieving diabetes remission can reduce the risk of microvascular complications and mitigate the burden of diabetes on healthcare systems. However, preventing weight regain is challenging in the long term. Strict glycemic control, particularly in the early stages of the disease, can reduce the subsequent risk of microvascular complications and specific macrovascular endpoints in the long run; however, its impact on cardiovascular and all-cause mortality remains controversial. New classes of antidiabetic agents, namely glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, have been shown to reduce cardiorenal risk and induce weight loss, in addition to effectively lowering blood glucose with a minimal risk of hypoglycemia. Recently, it has been debated whether weight loss or glycemic control should be the first priority in people with a recent diagnosis of type 2 diabetes. This article aims to discuss the debate from a clinical perspective, evaluate the advantages and disadvantages of each therapeutic strategy, and assess the impact of both approaches on the future risk of diabetic complications, based on the latest evidence. Given that both goals are equally important, the authors suggest that merging the two strategies, with the early and aggressive use of combination therapies consisting of glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, will confer maximum benefits in terms of weight loss and glycemic control, and will reduce the future risk of complications from diabetes. A personalized approach that takes into account specific patient characteristics, including age, sex, race, frailty, and cognitive status, among others, can lead to more effective diabetes care.

Twenty-first century epidemiology of dyslipidemia in Greece: EMENO national epidemiological study.

BACKGROUND: Greece was recently reclassified from low- to medium-risk country in terms of cardiovascular disease, with 27% of cardiovascular deaths attributed to hypercholesterolemia. EMENO nationwide survey (2013-2016) assessed the epidemiology of dyslipidemia in the general population in Greece. METHODS: A random sample of adults was drawn by multistage stratified random sampling based on 2011 census. Standardized questionnaires and blood tests for total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and triglycerides were used. Hypercholesterolemia was defined as TC ≥ 240/200 mg/dL and/or the use of lipid-lowering drugs, hyper-LDL-cholesterolemia as LDL-C ≥160/130/100 mg/dL and/or the use of drugs, hypo-HDL-cholesterolemia as HDL-C <40 mg/dL, and hypertriglyceridemia as triglycerides ≥150 mg/dL. Weighted analysis was applied to adjust for study design, age/sex distribution discrepancies between sample and population and nonresponse. RESULTS: Of 6,006 individuals recruited, 4,298 were analyzed (mean [SD] age 49.2 [18.5] years, men 48.5%, BMI 28.2 [5.7] kg/m2). Mean TC, LDL-C, HDL-C, and TG were 193.9 [44.4], 118.5 [37.6], 49.1 [14.9], and 130.8 [94.4] mg/dL, respectively. The prevalence of hypercholesterolemia was 27.6/52.4% for thresholds ≥240/200 mg/dL, and of hyper-LDL-cholesterolemia was 26.3/46.7/74% for thresholds ≥160/130/100 mg/dL, with no differences between sexes. The prevalence of hypo-HDL-cholesterolemia was 27.5% (men/women 38.1/17.5%, p < 0.001) and of hypertriglyceridemia was 27.8% (men/women 32.6/23.4%, p < 0.001). Lipid-lowering drugs were used by 14.1% of the participants (men/women 12.6/15.6%, p < 0.001). CONCLUSIONS: More than 50% of adults in Greece have some type of dyslipidemia (mainly TC ≥ 200 mg/dL) and 14% are treated. Nationwide programmes are needed to manage dyslipidemia and halt the increasing rate of cardiovascular disease in Greece.

Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH.

AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. METHODS: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. RESULTS: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. CONCLUSIONS: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

A Horse, a Jockey, and a Therapeutic Dilemma: Choosing the Best Option for a Patient with Diabetes and Coronary Artery Disease.

Current guidelines for the management of hyperglycemia recommend the use of agents with proven cardiovascular (CV) benefit in patients with type 2 diabetes (T2D) and established CV disease. Although both glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to reduce the risk of major adverse CV events (MACE) in high-risk populations with T2D, the ideal choice between the two classes for people with coronary artery disease remains controversial. SGLT2i reduce CV risk primarily through hemodynamic effects and changes in energy metabolism, making them the first choice in cases where heart failure or chronic kidney disease predominates. On the other hand, GLP-1 RA exert powerful anti-atherogenic properties that are the main drivers of their cardioprotection, and seem to have a consistent benefit in the atherosclerotic components of MACE. However, most people with diabetes and CV disease could take advantage of the complementary effects of the two drug categories on glycemic control, body weight, and diabetic complications. Future mechanistic studies and clinical head-to-head trials are expected to shed more light on this intriguing clinical dilemma and provide clear guidance for daily practice.

LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments.

BACKGROUND: The 2019 European guidelines (ESC/EAS) for the treatment of dyslipidaemias recommend more aggressive targets for low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). Current lipid-lowering treatment is often inadequate to achieve these targets. METHODS: Data from the HELLAS-FH registry were analysed to assess achievement of LDL-C targets in adults with FH based on the 2019 ESC/EAS guidelines. In patients who had not achieved LDL-C target, the maximally reduced LDL-C value was calculated after theoretical switch to rosuvastatin/ezetimibe 40/10 mg/day. The percentage of patients who remained candidates for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) was then calculated. RESULTS: Patients (n = 1694, mean age 50.8 ± 14.7 years) had LDL-C levels 242 ± 71 mg/dL (6.3 ± 1.8 mmol/L) at diagnosis. Most treated patients were receiving statins (97.5%) and about half were on additional ezetimibe (47.5%). Based on the 2019 ESC/EAS guidelines the percentage of patients achieving LDL-C goals was only 2.7%. Following theoretical up titration to rosuvastatin/ezetimibe 40/10 mg, LDL-C target achievement rate would increase to 5.9%. In this scenario, most patients (55.9%) would be eligible for PCSK9i treatment. Following theoretical administration of a PCSK9i, LDL-C target achievement rate would rise to 57.6%. However, 42.4% of patients would still be eligible for further LDL-C lowering treatment. CONCLUSIONS: Most FH patients do not reach new LDL-C targets even if on maximum intensity statin/ezetimibe treatment. In this case, more than half of FH patients are candidates for PCSK9i therapy and a considerable proportion may still require additional LDL-C lowering.

Prevalence of Non-coronary Heart Disease in Patients with Familial Hypercholesterolemia: An Analysis from the HELLAS-FH.

AIMS: Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH. MATERIALS & METHODS: This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). RESULTS: A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range - IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respectively. NAFLD was present in 24% of study participants. CONCLUSION: HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population.

Achieving low-density lipoprotein cholesterol targets as assessed by different methods in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and increased cardiovascular disease (CVD) risk. FH patients often have increased lipoprotein(a) [Lp(a)] levels, which further increase CVD risk. Novel methods for accurately calculating LDL-C have been proposed. METHODS: Patients with FH were recruited by a network of Greek sites participating in the HELLAS-FH registry. LDL-C levels were calculated using the Friedewald (LDL-CF) and the Martin/Hopkins (LDL-CM/H) equations as well as after correcting LDL-CM/H for Lp(a) levels [LDL-CLp(a)corM/H]. The objective was to compare LDL-C levels and target achievement as estimated by different methods in FH patients. RESULTS: This analysis included 1620 patients (1423 adults and 197 children). In adults at diagnosis, LDL-CF and LDL-CM/H levels were similar [235 ± 70 mg/dL (6.1 ± 1.8 mmol/L) vs 235 ± 69 mg/dL (6.1 ± 1.8 mmol/L), respectively; P = NS], while LDL-CLp(a)corM/H levels were non-significantly lower than LDL-CF [211 ± 61 mg/dL (5.5 ± 1.6 mmol/L); P = 0.432]. In treated adults (n = 966) both LDL-CF [150 ± 71 mg/dL (3.9 ± 1.8 mmol/L)] and LDL-CM/H levels [151 ± 70 mg/dL (6.1 ± 1.8 mmol/L); P = 0.746] were similar, whereas LDL-CLp(a)corM/H levels were significantly lower than LDL-CF [121 ± 62 mg/dL (3.1 ± 1.6 mmol/L); P < 0.001]. Target achievement as per latest guidelines in treated patients using the LDL-CM/H (2.5%) and especially LDL-CLp(a)corM/H methods (10.7%) were significantly different than LDL-CF (2.9%; P < 0.001). In children, all 3 formulas resulted in similar LDL-C levels, both at diagnosis and in treated patients. However, target achievement by LDL-CF was lower compared with LDL-CM/H and LDL-CLp(a)corM/H methods (22.1 vs 24.8 vs 33.3%; P < 0.001 for both comparisons). CONCLUSION: LDL-CLp(a)corM/H results in significantly lower values and higher target achievement rate in both treated adults and children. If validated in clinical trials, LDL-CLp(a)corM/H may become the method of choice to more accurately estimate 'true' LDL-C levels in FH patients.

Microsomal triglyceride transfer protein inhibitor (lomitapide) efficacy in the treatment of patients with homozygous familial hypercholesterolaemia.

AIMS: The aim of this study was to evaluate the effect of microsomal triglyceride transfer protein inhibitor (lomitapide) in patients with homozygous familial hypercholesterolaemia. METHODS AND RESULTS: In 12 homozygous familial hypercholesterolaemia patients treated with lipid-lowering drugs ± biweekly lipoprotein apheresis sessions (nine patients), daily lomitapide was added. The lipid profile (total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol) before and after lomitapide treatment was evaluated. The follow-up period with lomitapide treatment was 3-24 months (13.8 ± 7.9). The median baseline low-density lipoprotein cholesterol level was 900 mg/dl (348-1070), after lipid-lowering drugs therapy was 383.5 mg/dl (214-866) and after lipid-lowering drugs + time-averaged level was 288 mg/dl (183.7-716.6). The addition of lomitapide lowered low-density lipoprotein cholesterol levels further by 56.8% compared to lipid-lowering drugs alone (mean reduction 262, 95% confidence interval (105.5-418.7), p = 0.005) and by 54% (mean reduction 182.9, 95% confidence interval (-342 - -23), p = 0.031) comparing to lipid-lowering drugs + lipoprotein apheresis (time-averaged level). The time-averaged level of low-density lipoprotein cholesterol in lipid-lowering drugs + lipoprotein apheresis patients compared with lipid-lowering drugs + lomitapide was 54% in favour of lomitapide (p = 0.031). CONCLUSIONS: Treatment with lomitapide in homozygous familial hypercholesterolaemia patients has a beneficial effect with a constant decrease of low-density lipoprotein cholesterol by 57% compared with classical lipid-lowering therapy and by 54% compared with classical lipid-lowering therapy and time-averaged level of low-density lipoprotein cholesterol.

Canagliflozin and Amputation Risk: Evidence So Far.

The CANVAS program detected a 2-fold increased risk of lower limb amputation in patients treated with canagliflozin compared with those with placebo. This adverse effect was not confirmed in the CREDENCE trial. Moreover, randomized controlled trials with other agents in this class, dapagliflozin and empagliflozin, did not detect increased risk of amputation. Observational studies, cohort studies, and pharmacovigilance reports with sodium-glucose cotransporter 2 inhibitor (SGLT2i) have reported conflicting results. Whether this adverse event is a drug effect specific to canagliflozin, or a SGLT2i class effect, remains controversial. Until more evidence emerges, clinicians should avoid using SGLT2i, especially canagliflozin, in patients with previous amputations or existing foot ulceration.

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.

Effect of combined vitamin D administration plus dietary intervention on oxidative stress markers in patients with metabolic syndrome: A pilot randomized study.

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.

Characteristics and management of 1093 patients with clinical diagnosis of familial hypercholesterolemia in Greece: Data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

BACKGROUND AND AIMS: Although familial hypercholesterolemia (FH) is one of the most common genetic disorders, it remains largely underdiagnosed and undertreated. The Hellenic Atherosclerosis Society has established the Hellenic Familial Hypercholesterolemia (HELLAS-FH) Registry, part of the Familial Hypercholesterolemia Studies Collaboration (FHSC), to evaluate the characteristics and management of patients with FH in Greece. METHODS: Patients with diagnosed FH were recruited by a network of sites throughout Greece. The prevalence of cardiovascular disease (CVD) risk factors, as well as management of FH, was recorded. RESULTS: This interim analysis included 1093 patients (556 male; 950 adults). The median age of FH diagnosis was 42.2 years (interquartile range 27.2-53.0). A family history of CVD was present in 47.8%, while 21.1% of patients had a personal history of CVD. At diagnosis, low-density lipoprotein cholesterol (LDL-C) was 241 ±â€¯76 mg/dL in adults and 229 ±â€¯57 mg/dL in children. Overall, 63.1% of the patients were receiving hypolipidemic drug treatment, mainly statins, at inclusion in the registry. Mean LDL-C of patients receiving drug treatment was 154 ±â€¯76 mg/dL in adults and 136 ±â€¯47 mg/dL in children. The majority of treated patients (87.9%) did not achieve LDL-C targets. CONCLUSIONS: FH in Greece is characterized by a significant delay in diagnosis and a high prevalence of both family and personal history of established CVD. The vast majority of FH patients do not achieve LDL-C targets. Improved awareness and management of FH are definitely needed.

Prevalence, Identification, and Scouting for Familial Hypercholesterolaemia Including Registries.

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.

No effect of vitamin D supplementation on cardiovascular risk factors in subjects with metabolic syndrome: a pilot randomised study.

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.

An insight into familial hypercholesterolemia in Greece: rationale and design of the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

Familial hypercholesterolemia (FH) is the most common metabolic genetic disorder. It is estimated that around 13 million people worldwide have FH. At the same time, only 25% of FH patients have been diagnosed. Moreover, these patients are often undertreated. The true prevalence of FH in Greece is unknown, but it is estimated that there are at least 40,000 FH patients nationwide pointing to a prevalence of 1:250. Patients with FH are at a high risk for cardiovascular events and death at an early age. Therefore, prompt detection of these patients 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 promoting clinical practices, thus contributing to improved outcomes and reduction of healthcare costs. National registries of FH patients have been a success in the Netherlands, Spain and Wales. As Greece did not have a national FH registry, the Hellenic Atherosclerosis Society has organized, established and funded the Hellenic Familial Hypercholesterolemia (HELLAS-FH) national registry in order to promote a better understanding of FH in our country.

An insight into familial hypercholesterolemia in Greece: rationale and design of the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).

Familial hypercholesterolemia (FH) is the most common metabolic genetic disorder. It is estimated that around 13 million people worldwide have FH. At the same time, only 25% of FH patients have been diagnosed. Moreover, these patients are often undertreated. The true prevalence of FH in Greece is unknown, but it is estimated that there are at least 40,000 FH patients nationwide pointing to a prevalence of 1:250. Patients with FH are at a high risk for cardiovascular events and death at an early age. Therefore, prompt detection of these patients 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 promoting clinical practices, thus contributing to improved outcomes and reduction of healthcare costs. National registries of FH patients have been a success in the Netherlands, Spain and Wales. As Greece did not have a national FH registry, the Hellenic Atherosclerosis Society has organized, established and funded the Hellenic Familial Hypercholesterolemia (HELLAS-FH) national registry in order to promote a better understanding of FH in our country.

Dapagliflozin in patients with type 2 diabetes mellitus.

Dapagliflozin is a selective and reversible inhibitor of sodium-glucose linked transporter type 2 (SGLT2), which mediates approximately 90% of active renal glucose reabsorption in the early proximal tubule of the kidney. Dapagliflozin significantly reduces glucose reabsorption and decreases serum glucose concentration in an insulin-independent manner. The decrease of glucose reabsorption by dapagliflozin has also been associated with a reduction in body weight. Furthermore, the drug modestly reduces blood pressure levels through weight loss and its action as osmotic diuretic. Dapagliflozin has been approved as monotherapy in patients with type 2 diabetes mellitus (T2DM) who cannot tolerate metformin or in combination with other antidiabetic drugs, with the exception of pioglitazone due to the theoretical increased risk of bladder cancer. The drug should not be prescribed in patients with moderate or severe renal impairment or in patients at risk for developing volume depletion. Dapagliflozin is associated with increased incidence of genital and lower urinary tract infections, but these infections are usually mild to moderate and respond to standard antimicrobial treatment. Based on current evidence, dapagliflozin is a useful drug for patients with T2DM with a favorable safety profile. However, further research regarding the effects of dapagliflozin on cardiovascular outcomes is needed.

Combining rosuvastatin with angiotensin-receptor blockers of different PPARγ-activating capacity: effects on high-density lipoprotein subfractions and associated enzymes.

The effects of combining angiotensin-receptor blockers of different peroxisome proliferator-activated receptor γ-activating capacity with rosuvastatin on high-density lipoprotein (HDL) subfractions and associated enzymes in patients with mixed dyslipidemia, hypertension, and prediabetes were assessed. Patients (n = 151) were randomly allocated to rosuvastatin (10 mg/d) plus telmisartan 80 mg/d (RT group, n = 52) or irbesartan 300 mg/d (RI group, n = 48) or olmesartan 20 mg/d (RO group, n = 51). Total and intermediate HDL cholesterol (HDL-C) levels did not change in any group. Large HDL-C increased, while small HDL-C decreased significantly in all the groups (P = not significant between the groups). The mass of HDL lipoprotein-associated phospholipase A2 (HDL-Lp-PLA2) and the activities of paraoxonase 1 remained unchanged in all the groups. However, HDL-Lp-PLA2 activity increased only in the RT group (+21.4%; P < .01 vs baseline) and did not change in the RI (-4.3%; P = .005 vs RT group) and RO (+3.2%; P = .01 vs RT) groups. In conclusion, only the combination of rosuvastatin with telmisartan increased the possibly antiatherosclerotic HDL-Lp-PLA2 activity.