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Transition to menopause has been associated with an increased risk of cardiovascular disease (CVD), attributed mainly to atherogenic dyslipidemia. Whether lipoprotein (a) [Lp(a)], an independent cardiovascular risk factor, also contributes to menopause-associated CVD has not yet been clarified. The aim of this study was to systematically investigate and meta-analyze the best available evidence regarding the effect of menopause on Lp(a) concentrations.A comprehensive search was conducted in PubMed and Scopus databases up to March 8th, 2022. Data were expressed as weighted mean difference (WMD) with 95 % confidence intervals (CI). The ISeventeen studies were included in the qualitative and 15 in the quantitative analysis, yielding 4686 premenopausal and 8274 postmenopausal women. Lp(a) concentrations were lower in premenopausal than in postmenopausal women [WMD -3.77 (95 % CI -5.37, -2.18) mg/dl, p 0.001; ITransition to menopause may increase Lp(a) concentrations, although the effect of aging cannot be excluded by current data.

Hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are a worldwide health problem. Hypertensive disorders of pregnancy affect more than 10% of pregnancies and are associated with increased mortality and morbidity for both mother and fetus. Although patients' outcomes and family's experience will always be the primary concern regarding hypertensive complications during pregnancy, the economic aspect of this disease is also worth noting. Compared with normotensive pregnancies, those related with hypertension resulted in an excess increase in hospitalization and healthcare cost. Hence, the focus of this review is to analyze hypertensive disorders of pregnancy and to present practical tips with clear instructions for the clinical management of hypertensive disorders of pregnancy. This overview offers a detailed approach from the diagnosis to treatment and follow-up of a pregnant women with hypertension, evidence based, to support these instructions.

Global rates of obesity and type 2 diabetes mellitus (T2DM) are increasing globally concomitant with a rising prevalence of sleep deprivation and sleep disorders. Understanding the links between sleep, obesity and T2DM might offer an opportunity to develop better prevention and treatment strategies for these epidemics. Experimental studies have shown that sleep restriction is associated with changes in energy homeostasis, insulin resistance and β-cell function. Epidemiological cohort studies established short sleep duration as a risk factor for developing obesity and T2DM. In addition, small studies suggested that short sleep duration was associated with less weight loss following lifestyle interventions or bariatric surgery. In this article, we review the epidemiological evidence linking sleep duration to obesity and T2DM and plausible mechanisms. In addition, we review the impact of changes in sleep duration on obesity and T2DM.

The COVID-19 pandemic has posed new challenges to the management of the ever-growing group of patients with Diabetes Mellitus (DM). An important question to be answered is which, if any, specific glucose-lowering therapy is associated with worse or better COVID-19 related outcomes for patients with DM. Physicians had to make such management decisions in the absence of robust scientific evidence so far. After nearly two years into the pandemic, there are now a fair number of published studies comparing the premorbid or in-hospital use of certain anti-diabetic medications and relating them to certain COVID-19 outcomes, and there are also a number of published recommendations for the management of people with DM during the pandemic. The purpose of this review is to examine the relationship between the different classes of antidiabetic medications and COVID-19 related outcomes, as well as to make evidence-based recommendations regarding the use of glucose-lowering therapies during acute COVID-19 infection.

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. Conclusions: 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.

Network Meta-analysis

Arterial stiffness has been associated with cardiovascular events and correlated with cardiovascular risk factors. In the new guidelines of the European Society of Hypertension, the evaluation of arterial stiffness, and specifically carotid-femoral pulse wave velocity (c-f PWV), was taken into account for the detailed screening of the hypertensive population. Despite the importance of arterial stiffness as a target organ damage, the measurement is time-consuming, not practical, needs expensive equipment and experienced staff. For all these reasons, c-f PWV is not recommended for the everyday clinical practice and its current use is restricted for research purposes. The importance of arterial properties in clinical practice and cardiovascular prevention is well known. Hence, the estimation of arterial stiffness and vascular health based on parameters that affect arterial stiffness, but without the use of a machine, is a new promising field. Furthermore, the relationship between age-related MRI abnormalities as well as ultrafast ultrasound with vascular effect gives a new promise for future vascular aging assessment.

Blood pressure (BP) phenotypes have a prognostic significance for target organ damage in long-term studies. However, it remains uncertain whether a single baseline phenotype classification is reproducible over time and represents accurately the patients' BP status. The aim of this study was to systematically investigate the reproducibility of masked hypertension and office-based hypertension either with ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM). PubMed, Cochrane Library and Web of Science were searched to identify studies with paired baseline office BP and ABPM or HBPM measurements at two timepoints. The outcome of the analysis was the individual phenotype reproducibility between the baseline and follow-up timepoints. The used effect measure was Cohen's kappa coefficient. We found 15 studies eligible for the meta-analysis enrolling a total of 5729 patients. The reproducibility of masked hypertension was better with ABPM, kappa reliability test: 0.41 [95% confidence interval (CI): 0.32-0.49], than with HBPM, kappa reliability test: 0.26 (95% CI: 0.10-0.40). The reproducibility of office-based hypertension with both methods was low, indicating slight agreement. Kappa reliability test was slightly better with ABPM (κ: 0.27, 95% CI: 0.12-0.41) than with HBPM (κ: 0.18, 95% CI: 0.08-0.27). This systematic review and meta-analysis show a slight to fair reproducibility of masked hypertension and office-based hypertension assessed through ABPM and HBPM. Considering that poor reproducibility may be a result of office BP measurements, an ABPM/HBPM-based strategy should be established for the evaluation and treatment of patients with masked hypertension or office-based hypertension.

Diabetes mellitus (DM) is an established risk factor for atherosclerotic cardiovascular disease (CVD), and patients with DM are at a two to four-fold higher cardiovascular risk, including myocardial infraction, unstable angina, stroke, and heart failure. All of the above have arisen interest in CVD preventive strategies by the use of non-invasive methods, such as risk scores. The most common approach is to consider DM as a CVD equivalent and, therefore, to treat patients with DM in a similar way to those who required secondary CVD prevention. However, this approach has been disputed as all patients with DM do not have the same risk for CVD, and since other potentially important factors within the context of DM, such as DM duration, presence of albuminuria, and comorbidities, should be taken into consideration. Thus, the second and third approach is the application of risk models that were either developed initially for the general population or designed specifically for patients with DM, respectively. This review summarizes the evidence and implications for clinical practice regarding these scores. Up to date, several models that can be applied to the diabetic population have been proposed. However, only a few meet the minimum requirement of adequate external validation. In addition, moderate discrimination and poor calibration, which might lead to inaccurate risk estimations in populations with different characteristics, have been reported. Therefore, future research is needed before recommending a specific risk model for universal clinical practice in the management of diabetes.

Background: Atrial Fibrillation (AF) has become a major global health concern and is associated with an increased risk of poor outcomes. Identifying risk factors in patients with AF can be challenging, given the high burden of comorbidities in these patients. Risk stratification schemes appear to facilitate accurate prediction of outcomes and assist therapeutic management decisions. Objective: To summarize current evidence on risk stratification scores for patients with AF. Results: Traditional risk models rely heavily on demographics and comorbidities, while newer tools have been gradually focusing on novel biomarkers and diagnostic imaging to facilitate more personalized risk assessment. Several studies have been conducted to compare existing risk schemes and identify specific patient populations in which the prognostic ability of each scheme excels. However, current guidelines do not appear to encourage the implementation of risk models in clinical practice, as they have not incorporated new ones in their recommendations for the management of patients with AF for almost a decade. Conclusion: Further work is warranted to analyze new reliable risk stratification schemes and optimally implement them into routine clinical life.

Lipoprotein(a) [Lp(a)] is a cardiovascular factor, for which there is no approved specific lowering treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to have lowering effects on Lp(a). Aim of this systematic review is to synthesize the current literature and quantify the effects of PCSK9 inhibitors on the serum Lp(a) levels in human subjects. Double-blind, phase 2 or 3, randomized-controlled trials comparing PCSK9 inhibitors (alirocumab or evolocumab) to placebo and/or ezetimibe and/or other lipid-lowering therapy were deemed eligible for inclusion. We searched MEDLINE (via PubMed), CENTRAL, Scopus, and Web of Science as of 17 June 2020. Quality assessment was performed using the Revised Cochrane risk-of-bias tool for randomized trials. Forty-three studies were identified (64,107 patients randomized) and 41 studies were included in the quantitative analysis. PCSK9 inhibitors reduced Lp(a) levels by -26.7% (95% CI, -29.5% to -23.9%) with a significant heterogeneity within studies. There was significant difference in Lp(a) change from baseline according to comparator (placebo: mean -27.9%; 95% CI, -31.1% to -24.6% vs. ezetimibe: mean, -22.2%; 95% CI, -27.2% to -17.2%; P = 0.04) and duration of treatment (≤12 weeks: mean, -30.9%; 95% CI, -34.7% to -27.1% vs. >12 weeks: mean, -21.9%; 95% CI, -25.2% to -18.6%; P < 0.01). Meta-regression analysis showed that only the mean percentage change from baseline low-density lipoprotein cholesterol due to the intervention is significantly associated with the effect size difference (P < 0.0001). PCSK9 inhibitors reduced low-density lipoprotein cholesterol by -54% (95% CI -57.6% to -50.6%). There is substantial efficacy of the currently approved PCSK9 inhibitors in the lowering of Lp(a) levels. Dedicated randomized controlled trials are needed to establish the benefit of this intervention.

Background Obstructive sleep apnoea (OSA) is very common in patients with type 2 diabetes (T2D). We and others have shown that OSA was associated with diabetes-related microvascular complications in patients with T2D in cross-sectional and longitudinal studies and that compliance with continuous positive airway pressure (CPAP) reduced the progression of microvascular complications. Hence, we hypothesised that adequate CPAP reduces the development of microvascular complication in patients with T2D. Methods SLEEP T2D is a cohort study with embedded feasibility, open-label, parallel-arm, randomised control trial (RCT) over 2 years. The primary aim is the feasibility of conducting a definitive RCT assessing the impact of CPAP on chronic kidney disease and other microvascular complications in patients with T2D. The main parameters are to assess willingness of participants to be randomised, follow-up rates, CPAP adherence/compliance, to optimise the choice of outcome measures for a substantive trial, and to identify the parameters for sample size calculations. The secondary aims of the study are related to the impact of CPAP, sleep-related disorders, and sleep chronotype on a variety of diabetes-related end points. The study participants were recruited from the T2D services in multiple NHS trusts across England. The main exclusion criteria for the cohort study are as follows: T1D, eGFR 2, known OSA, active malignancy or chronic kidney disease from reasons other than diabetes, pregnancy, professional drivers, and a history of falling asleep whilst driving within last 2 years. The main exclusion criteria from the RCT were as follows: Apnoea-Hypopnoea Index TM, Resmed). Discussion The feasibility RCT will help us design the future RCT to assess the impact of CPAP on diabetes-related microvascular complications. The cohort study will generate preliminary data regarding the impact of sleep quality, duration, and chronotype on diabetes-related outcomes which could lead to further mechanistic and interventional studies. Trial registration ISRCTN, ISRCTN12361838. Registered 04 April 2018, Protocol version: v5.0 02.12.19.

BACKGROUND AND AIM Νon-alcoholic fatty liver disease (NAFLD) is estimated to be the most common cause of end-stage liver disease in the next years. Vitamin E has shown beneficial effects as a possible "scavenger" of oxidative stress products, which play a major role in pathogenesis of the disease. The purpose of the present meta-analysis is to investigate the effects of vitamin E supplementation in biochemical and histological parameters in adult patients with NAFLD. METHODS Literature search was performed in major electronic databases (MEDLINE, CENTRAL, and Embase) up to June 2020 for randomized clinical trials, which examined vitamin E versus placebo treatment in adults with NAFLD. Changes in liver enzymes were considered as primary outcomes while changes in histological, biochemical, and metabolic parameters as secondary. Quality of evidence was assessed through risk of bias according to the Cochrane risk of bias tool. RESULTS Eight studies were included in qualitative analysis and seven in quantitative analysis. Vitamin E reduced the values of liver enzymes compared with placebo (-7.37 IU/L, 95% confidence interval: -10.11 to -4.64 for alanine aminotransferase, and -5.71 IU/L, 95% confidence interval: -9.49 to -1.93 for aspartate aminotransferase). Additionally, vitamin E improved statistically significantly liver pathology in every individual histological parameter as well as low-density lipoprotein cholesterol, fasting blood glucose, and serum leptin values. CONCLUSIONS Vitamin E can improve biochemical and histological characteristics of NAFLD patients, especially of non-alcoholic steatohepatitis patients. The results indicate that vitamin E could be a promising choice and be considered as a treatment option in patients with NAFLD.

Sickle cell disease (SCD) is associated with increased risk of cardiovascular disease, although blood pressure (BP) levels have been reported to be lower in SCD patients compared to general population. Aims of the present study were to investigate the prevalence of BP phenotypes and levels of arterial stiffness in pediatric patients with SCD and to assess the differences with children at risk for hypertension. We included in the study 16 pediatric SCD (HbS/β‐thalassemia, S/β‐thal) patients and 16 consecutive children at risk for hypertension referred to our hypertension clinic that served as high‐risk controls. All patients underwent ambulatory BP monitoring and measurement of carotid‐femoral pulse wave velocity (PWV). S/β‐thal patients had lower office systolic BP than the high‐risk control group (115.43 ± 10.03 vs 123.37 ± 11.92, P = .05) but presented similar levels of day and night ambulatory BP. Office hypertension was found in 12.5% of the S/β‐thal patients and in 43.8% of the high‐risk controls (P = .06), while 18.8% of the S/β‐thal patients and 25% of the high‐risk controls presented hypertension by ambulatory BP levels (P = .21). All of the S/β‐thal patients with ambulatory hypertension had night hypertension (one combined night and day hypertension) with office normotension (masked hypertension). S/β‐thal patients and high‐risk controls presented equal prevalence of masked hypertension (18.8%). Children and adolescents with S/β‐thal present similar prevalence of BP phenotypes and levels of PWV with children at risk for hypertension. A significant number of children and adolescents with S/β‐thal may have masked nighttime hypertension despite normal office BP levels.

Background: Anticoagulation in patients with pulmonary embolism. Objective: To identify how non-vitamin K antagonist oral anticoagulants are associated with multiple outcomes in patients with pulmonary embolism. Methods: We performed a systematic search of systematic reviews via multiple electronic databases from inception to August 19th, 2019, without language restriction. Two authors independently extracted data and assessed the methodological quality of the included systematic reviews using the ROBIS tool. Results: We found twelve systematic reviews. Eleven SRs collected their data from randomized clinical trials and one from observational studies. All the included studies were published between 2014 and 2019 in English. The methodological quality of the 12 systematic reviews was low to high. None of the systematic reviews, which are included in our overview of systematic reviews, has evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. Conclusion: This is the first effort to summarize evidence about non-vitamin K antagonist oral anticoagulants in an overview of systematic reviews focusing exclusively on patients with pulmonary embolism. The evidence suggests that the non-vitamin K antagonist oral anticoagulants seem to be more effective and safer than a dualdrug approach with LMWH- VKA.

Backround: The relationship between obesity and hypertension has been established in both adults and children. The combination of obesity, hypertension and other cardiovascular risk factors significantly increases the likelihood of adverse cardiovascular effects and raises concerns about aggressive treatment strategies. Objective: Despite the impressive elements which indicate an important role for excessive weight gain in increasing blood pressure, not all obese patients are hypertensive. A subgroup of obese people may not develop hypertension. Furthermore, masked hypertension occurs more common among obese patients, and body fat distribution has a major role in the development of hypertension. Methods: We conducted a research of the relevant literature regarding obesity-induced hypertension and possible treatment strategies. Results: Successful weight loss is correlated with blood pressure reduction and requires a multidisciplinary approach that includes personalized dietary interventions combined with regular exercise and cognitive behavioral therapy. Conclusion: Pharmacological therapy may be considered as part of a comprehensive obesity management strategy. More research and new treatment therapies are required in this field.

The present systematic review and meta-analysis investigated the effects of hydralazine compared with other antihypertensive drugs in maternal, perinatal and neonatal outcomes of pregnant women with hypertensive disorders. Twenty studies with 1283 participants were included. Of them, 626 received hydralazine and 657 other antihypertensive treatments, such as labetalol, nifedipine, ketanserin, diazoxide, urapidil, isradipine and epoprostenol. Women receiving hydralazine had higher heart rate (WMD: 13.4, 95%CI: 0.1 to 26.8 beats/min), increased number of adverse effects (RR: 1.21, 95%CI: 1.01 to 1.45) and gave birth to neonates of lower birthweight (WMD: 13.4, 95%CI: 0.1 to 26.8 beats/min) compared with other antihypertensive treatments at the end of follow-up. When studies, which used antihypertensive agents that are no longer indicated for hypertension in pregnancy, were excluded in the sensitivity analyses, hydralazine found not to have a statistically significant difference compared with labetalol and nifedipine regarding the reduction of maternal blood pressure (WMD: 1.72, 95%CI: −1.47 to 4.9 mmHg for systolic, WMD: 0.26, 95%CI: −1.75 to 2.28 mmHg for diastolic), maternal heart rate (WMD: 13.56, 95%CI: −5.62 to 32.74 beats/min), low birthweight (WMD: −88.62, 95%CI: −243.24 to 66 beats/min) and adverse events (RR: 1.19, 95%CI: 0.99 to 1.43). Hydralazine seems not to be inferior compared to labetalol and nifedipine for safety and efficacy.

Η παρούσα μελέτη συγκρίνει τη διαγνωστική ακρίβεια των μεθόδων καταγραφής της αρτηριακής πίεσης (ΑΠ)- στο ιατρείο, στο σπίτι, με την 24ωρη περιπατητική καταγραφή (ABPM)- για τον προσδιορισμό της πρώιμης αγγειακής γήρανσης (EVA) και σκοπεύει στη δημιουργία ενός μοντέλου πρόβλεψης της EVA στον υπερτασικό πληθυσμό. Μέθοδοι: 282 συμμετέχοντες (39,7% άνδρες) ηλικίας 56,8 ± 15,8 ετών συμπεριλήφθηκαν στη μελέτη. Η ΑΠ μετρήθηκε στο ιατρείο, 7 συνεχόμενες ημέρες στο σπίτι και με την 24ωρη ABPM σε μία τυπική εργάσιμη ημέρα. Η καρωτιδο-μηριαία ταχύτητα σφυγμικού κύματος (c-f PWV) μετρήθηκε σε όλους τους συμμετέχοντες. Η EVA καθορίστηκε ως οι τιμές της c-f PWV που είναι υψηλότερες από τις αναμενόμενες για την ηλικία, βάση των δεδομένων για τον Ευρωπαϊκό πληθυσμό. Αποτελέσματα: Στη μονοπαραγοντική ανάλυση, η EVA συσχετίστηκε στατιστικά σημαντικά με την συστολική ΑΠ ιατρείου και τη καρδιακή συχνότητα ιατρείου, το μέσο όρο της συστολικής και διαστολικής ΑΠ από την 24ωρη ABPM και από τη καρδιακή συχνότητα της 24ωρη ABPM. Η περιοχή κάτω από την καμπύλη ROC για την πρόβλεψη της EVA ήταν 0,624 (95% CI 0,551-0,697, p

BACKGROUND AND OBJECTIVES In 2017, the American Academy of Pediatrics (AAP) recommended new blood pressure (BP) thresholds for the diagnosis of hypertension in children and adolescents. We assessed the impact of the AAP guideline, as compared to the Fourth Report and the 2016 European Society of Hypertension guidelines (ESH), on the prevalence of hypertension and the detection of left ventricular hypertrophy (LVH). METHODS We systematically searched for studies evaluating the impact of the 2017 AAP guidelines on the prevalence of hypertension and LVH compared with the Fourth Report or the 2016 ESH guidelines. Meta-analysis was performed to compare the overall risk of LVH between the guidelines. We used a random-effects model to synthesize quantitative data. RESULTS We included 18 observational studies in the systematic review with an overall moderate to high risk of bias. The AAP guideline identified more children with hypertension than the Fourth Report and the ESH guidelines. In the meta-analysis of three observational studies, the guidelines revealed similar associations with LVH [odds ratio (OR) = 3.89, 95% confidence interval (95% CI) 1.68-8.99 for AAP and OR = 3.19, 95% CI 1.14-8.88 for Fourth Report/ESH guidelines]. Qualitative analysis of two observational studies revealed similar predictive value of the guidelines for LVH in adult life. CONCLUSION Despite the higher prevalence of hypertension frequently reported by the adoption of AAP guideline BP thresholds compared with Fourth Report and the ESH guidelines, the new thresholds have not been proved to advance assessment of cardiovascular risk in terms of LVH currently the most accepted subclinical marker in youth.

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.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.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.Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

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.

Background Miscarriages affect up to a fifth of all pregnancies and are associated with substantial psychological morbidity. However, their relationship with cardiometabolic risk factors is not well known. Therefore, in this study we aimed to estimate the burden of cardiovascular risk factors including diabetes mellitus (type 1 or 2) and hypertension in women with miscarriage compared to women without a record of miscarriage. Methods A population-based retrospective cohort study was conducted using IVQIA Medical Research Data UK (IMRD-UK) between January 1995 and May 2016, an anonymised electronic health records database that is representative of the UK population. A total of 86,509, 16–50-year-old women with a record of miscarriage (exposed group) were matched by age, smoking status, and body mass index to 329,865 women without a record of miscarriage (unexposed group). Patients with pre-existing hypertension and diabetes were excluded. Adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95% CI) for diabetes and hypertension were estimated using multivariable Poisson regression models offsetting for person-years follow-up. Results The mean age at cohort entry was 31 years and median follow up was 4.6 (IQR 1.7–9.4) years. During the study period, a total of 792 (IR 1.44 per 1000 years) and 2525 (IR 1.26 per 1000 years) patients developed diabetes in the exposed and unexposed groups, respectively. For hypertension, 1995 (IR 3.73 per 1000 years) and 1605 (IR 3.39 per 1000 years) new diagnoses were recorded in the exposed and unexposed groups, respectively. Compared to unexposed individuals, women with a record miscarriage were more likely to develop diabetes (aIRR = 1.25, 95% CI: 1.15–1.36; p Conclusions Women diagnosed with miscarriage were at increased risk of developing diabetes mellitus and hypertension. Women with history of miscarriage may benefit from periodic monitoring of their cardiometabolic health.

Glucagon-like peptide 1 receptor agonists (GLP1-RA) are prominent agents in the therapeutics of type 2 diabetes mellitus due to their exemplary efficacy in both preprandial and postprandial glycemia, their safety, low risk of hypoglycemia, their multilevel pathophysiological superiority, weight loss and importantly the observed benefits in cardiovascular disease reduction. Their major drawback is the subcutaneous route of administration, constituting a barrier to adoption and reason for treatment discontinuation. Thus, the development of an oral GLP1-RA agent would promote medication adherence and quality of life, further consolidating its beneficial effects in real-life clinical practice. However, this task is hampered by suboptimal gastrointestinal protein absorption. Yet, the introduction of oral semaglutide, a modified form of semaglutide with the addition of a carrier sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, may have provided a safe and effective way to reach systemic circulation while other molecules are in development. Whether this molecule still has the impressive cardiovascular effects demonstrated with the use of its precursor remains to be explored. However, to date, its efficacy and safety have already been showcased in a randomized trial. More research is warranted in order to further consolidate these findings across different type 2 diabetes mellitus (T2DM) subpopulations, and adequately powered studies with a longer follow-up that would allow the exploration of microvascular and macrovascular complications are needed. Finally, studies comparing oral semaglutide and similar molecules with other currently established antidiabetic agents to evaluate the relative efficacy, the cost-effectiveness and further understand its place in T2DM therapeutic algorithm are needed. This review focuses on the development of oral GLP1-RA agents and summarizes the challenges, milestones and expected benefits associated with a successful introduction.

OBJECTIVE We assessed the performance of the simplified American Academy Pediatrics (AAP) 2017 guideline table and a simplified table based on the Fourth Report blood pressure (BP) reference tables for high BP screening compared with the European Society Hypertension 2016 guideline diagnostic thresholds. METHODS We obtained data from a cross-sectional, school-based screening study in north Greece during 2013-2016. BP was measured by mercury sphygmomanometer. The simple tables' performance for high BP was assessed by receiver operator characteristic curve analysis, area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS The study population included 1846 children aged 6-12 years and 986 adolescents aged 13-18 years. Compared with the European Society Hypertension 2016 classification, the AAP 2017 simple table showed AUC 0.93, sensitivity 95.5%, specificity 91.6%, PPV 35.9%, and NPV 99.7%, whereas the Fourth Report one showed AUC 0.96, sensitivity 99.2%, specificity 93.2%, PPV 42.1%, and NPV 99.9%. Comparing the prevalence of high BP by the two tables, we found agreement in 96.9% of the participants, and disagreement in 3.1% (kappa coefficient = 0.85, P

This study investigated the impact of body composition in the arterial stiffness of children with chronic kidney disease (CKD). Fat mass (FM), fat tissue index (FTI), fat-free mass (FFM), fat-free tissue index (FFTI), and FFTI/FTI were measured in 26 patients and 25 healthy controls by bio-impedance analysis. Data on patient’s body mass index (BMI) for height-age, serum albumin, glomerular filtration rate (GFR), blood pressure status, and pulse wave velocity (PWV) were collected in patients. Patients presented lower levels of FM and FFM compared to healthy controls (p = 0.04 and p = 0.055 respectively). In patient group, BMI height-age z-score was positively correlated to FTI (r2 = 0.574, p

Carotid-femoral pulse wave velocity (c-f PWV) is considered to be one of the main factors affecting CV risk in the hypertensive population and has been included to the detailed screening of the hypertensive patients according to the ESH guidelines. Despite the large number of studies proving the correlation of blood pressure (BP) and c-f PWV as well as arterial stiffness, there are only few studies to show which BP measurement method can better predict arterial stiffness. Generally, these studies express the superiority of ABPM in the prediction of c-f PWV and early vascular aging (EVA). Furthermore, while guidelines recommend measuring c-f PWV in the hypertensive population, on the other hand it is difficult, time consuming and expensive to measure arterial stiffness in the everyday clinical practice, limiting its use only for experts. These limitations lead to the creation of a new score, the Early Vascular Aging Ambulatory score (EVAAs), which uses parameters from the ABPM and other cardiovascular risk factors in order to identify the possibility of each patient to have EVA. The score should be further studied for its accuracy in a larger population, as well for predicting hard end points in prospective studies.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Management of cardiovascular risk factors, particularly hypertension and dyslipidemia, has been shown to reduce cardiovascular morbidity and mortality. However, current guidelines recommend adjusting the intensity of blood pressure- and lipid-lowering treatment according to the cardiovascular risk of the patient. Therefore, cardiovascular risk prediction is a sine qua non for optimizing cardiovascular prevention strategies, particularly in patients without established CVD or type 2 diabetes mellitus (T2DM). As a result, several cardiovascular risk prediction equations have been developed. Nevertheless, it is still unclear which is the optimal prediction risk equation. In the present review, we summarize the current knowledge regarding the accuracy of the most widely used cardiovascular risk prediction equations. Notably, most of these risk scores have not been validated in external cohorts or were shown to over- or underestimate risk in populations other than those in which they derive. Accordingly, country-specific risk scores, where available, should be preferred for cardiovascular risk stratification.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are drugs commonly used for the treatment of hypertension. However, studies on their comparative efficacy have not been extensively investigated. The current systematic review and network meta-analysis studied the comparative efficacy of the two antihypertensive treatment categories in reducing blood pressure, mortality, and morbidity in essential hypertension patients. A literature search was carried out in Medline and Cochrane Central Register of Controlled Trials for placebo- and active-controlled, double-blind randomized clinical trials, which had reported blood pressure effects, mortality, and/or morbidity. Blood pressure results were found in 30 studies with 7370 participants and 8 studies with 25,158 participants with mortality/morbidity results included in the analysis. The two drug classes had similar effectiveness in lowering systolic (weighted mean difference (WMD): 0.59, 95% CI: -0.21 to 1.38) and diastolic blood pressure (WMD: 0.62, 95% CI: -0.06 to 1.30), all-cause mortality (risk ratio (RR)): 0.96, 95% CI 0.80 to 1.14), cardiovascular mortality (RR: 0.87, 95% CI 0.67 to 1.14), fatal and non-fatal myocardial infarction (RR: 1.02, 95% CI 0.75 to 1.37) and stroke (RR: 1.13, 95% CI 0.87 to 1.46). Angiotensin-converting enzyme inhibitors were more helpful in the prevention and/or the hospitalization for heart failure than angiotensin receptor blockers (RR: 0.71, 95% CI 0.54 to 0.93). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were similarly effective in decreasing blood pressure, mortality, and morbidity in essential hypertension. Angiotensin-converting enzyme inhibitors were more protective in the advancement and/or hospitalization of the hypertensive patient for heart failure than angiotensin receptor blockers.

OBJECTIVE To investigate the relationship between social deprivation and incident diabetes-related foot disease (DFD) in newly diagnosed patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A population-based open retrospective cohort study using The Health Improvement Network (1 January 2005 to 31 December 2019) was conducted. Patients with type 2 diabetes free of DFD at baseline were stratified by Townsend deprivation index, and risk of developing DFD was calculated. DFD was defined as a composite of foot ulcer (FU), Charcot arthropathy, lower-limb amputation (LLA), peripheral neuropathy (PN), peripheral vascular disease (PVD), and gangrene. RESULTS A total of 176,359 patients were eligible (56% men; mean age 62.9 [SD 13.1] years). After excluding 26,094 patients with DFD before/within 15 months of type 2 diabetes diagnosis, DFD incidentally developed in 12.1% of the study population over 3.27 years (interquartile range 1.41–5.96). Patients in the most deprived Townsend quintile had increased risk of DFD compared with those in the least deprived (adjusted hazard ratio [aHR] 1.22; 95% CI 1.16–1.29) after adjusting for sex, age at type 2 diabetes diagnosis, ethnicity, smoking, BMI, HbA1c, cardiovascular disease, hypertension, retinopathy, estimated glomerular filtration rate, insulin, glucose/lipid-lowering medication, and baseline foot risk. Patients in the most deprived Townsend quintile had higher risk of PN (aHR 1.18; 95% CI 1.11–1.25), FU (aHR 1.44; 95% CI 1.17–1.77), PVD (aHR 1.40; 95% CI 1.28–1.53), LLA (aHR 1.75; 95% CI 1.08–2.83), and gangrene (aHR 8.49; 95% CI 1.01–71.58) compared with those in the least. CONCLUSIONS Social deprivation is an independent risk factor for the development of DFD, PN, FU, PVD, LLA, and gangrene in newly diagnosed patients with type 2 diabetes. Considering the high individual and economic burdens of DFD, strategies targeting patients in socially deprived areas are needed to reduce health inequalities.

Differentiated thyroid cancer (DTC) represents the most common form of thyroid neoplasms and is becoming increasingly prevalent. Evidence suggests a possible relationship between DTC diagnosis and subsequent atrial fibrillation (AF). If confirmed, this may present an alarming health risk (AF) in an otherwise condition with a relatively good prognosis (DTC). The aim of this systematic review and meta-analysis is to provide for the first time a pooled estimate of AF incidence in DTC patients in comparison to healthy controls. A detailed search in electronic databases, clinical trial registries and grey literature was performed to identify studies reporting the incidence of AF in DTC patients. Newcastle–Ottawa quality assessment scale was used to assess study quality. We used a random effects (RE) generalized linear mixed model (GLMM) in pooling of individual studies and also calculated a prediction interval for the estimate of a new study. Six observational studies met the eligibility criteria, which included totally 187,754 patients with DTC and 199,770 healthy controls. The median follow-up period was 4.3 to 18.8 years; the incidence rate of AF was 4.86 (95% CI, 3.29 to 7.17, I2 = 96%) cases per 1000 person-years, while the incidence rate ratio was 1.54 (95% CI, 1.44 to 1.65, I2 = 0%, 95% PI, 1.33 to 1.78).This is the first meta-analysis to confirm that patients with DTC are at a high risk for developing AF, which may be attributed to a state of iatrogenic hyperthyroidism due to long-term thyrotropin suppression therapy.

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.

Background Attempts to utilize eHealth in diabetes mellitus (DM) management have shown promising outcomes, mostly targeted at patients; however, few solutions have been designed for health care providers. Objective The purpose of this study was to conduct a feasibility project developing and evaluating a mobile clinical decision support system (CDSS) tool exclusively for health care providers to manage chronic kidney disease (CKD) in patients with DM. Methods The design process was based on the 3 key stages of the user-centered design framework. First, an exploratory qualitative study collected the experiences and views of DM specialist nurses regarding the use of mobile apps in clinical practice. Second, a CDSS tool was developed for the management of patients with DM and CKD. Finally, a randomized controlled trial examined the acceptability and impact of the tool. Results We interviewed 15 DM specialist nurses. DM specialist nurses were not currently using eHealth solutions in their clinical practice, while most nurses were not even aware of existing medical apps. However, they appreciated the potential benefits that apps may bring to their clinical practice. Taking into consideration the needs and preferences of end users, a new mobile CDSS app, “Diabetes & CKD,” was developed based on guidelines. We recruited 39 junior foundation year 1 doctors (44% male) to evaluate the app. Of them, 44% (17/39) were allocated to the intervention group, and 56% (22/39) were allocated to the control group. There was no significant difference in scores (maximum score=13) assessing the management decisions between the app and paper-based version of the app’s algorithm (intervention group: mean 7.24 points, SD 2.46 points; control group: mean 7.39, SD 2.56; t37=–0.19, P=.85). However, 82% (14/17) of the participants were satisfied with using the app. Conclusions The findings will guide the design of future CDSS apps for the management of DM, aiming to help health care providers with a personalized approach depending on patients’ comorbidities, specifically CKD, in accordance with guidelines.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a new antihyperglycemic class with the demonstrated advantage of reducing major adverse cardiovascular events (MACE) among individuals with type 2 diabetes (T2DM), atherosclerotic cardiovascular disease, or high cardiovascular risk. Objective: Τo summarize the evidence of systematic reviews (SRs) that assess MACE (cardiovascular mortality, nonfatal myocardial infarction, and stroke) and hospitalizations for heart failure in GLP-1RAs-treated patients and to evaluate possible overlap in pertinent SRs. Methods: We performed a comprehensive search via MEDLINE, Cochrane Library, and PROSPERO databases up to February 23, 2020, for SRs examining cardiovascular outcomes of GLP-1RAs in T2DM patients. Three independent authors extracted data and assessed the methodological quality of the included SRs using the ROBIS tool. Results : We found 37 SRs – published between 2009 and 2020 in English – of which 35 collected data only from randomized clinical trials while two from observational studies as well. The methodological quality of the 37 SRs ranged from low to high, while only 3 have evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. All the included SRs showed cardiovascular safety of GLP-1RAs while the latest ones demonstrated a reduction in composite MACE endpoint as well as its every individual component and heart failure hospitalizations. Conclusion: In the first overview of SRs about cardiovascular outcomes of GLP-1RAs, they proved favorable effects on reducing cardiovascular events in T2DM patients. There are, however, many overlapping reviews based on relatively few cardiovascular outcomes trials.