Navigating between Scylla and Charybdis: challenges and strategies for implementing guideline-directed medical therapy in heart failure with reduced ejection fraction.

Guideline-directed medical therapy (GDMT) has the potential to reduce the risks of mortality and hospitalisation in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data indicate that many patients with HFrEF do not receive optimised GDMT, which involves several different medications, many of which require up-titration to target doses. There are many challenges to implementing GDMT, the most important being patient-related factors (comorbidities, advanced age, frailty, cognitive impairment, poor adherence, low socioeconomic status), treatment-related factors (intolerance, side-effects) and healthcare-related factors that influence availability and accessibility of HF care. Accordingly, international disparities in resources for HF management and limited public reimbursement of GDMT, coupled with clinical inertia for treatment intensification combine to hinder efforts to provide GDMT. In this review paper, authors aim to provide solutions based on available evidence, practical experience, and expert consensus on how to utilise evolving strategies, novel medications, and patient profiling to allow the more comprehensive uptake of GDMT. Authors discuss professional education, motivation, and training, as well as patient empowerment for self-care as important tools to overcome clinical inertia and boost GDMT implementation. We provide evidence on how multidisciplinary care and institutional accreditation can be successfully used to increase prescription rates and adherence to GDMT. We consider the role of modern technologies in advancing professional and patient education and facilitating patient-provider communication. Finally, authors emphasise the role of novel drugs (especially sodium-glucose co-transporter 2 inhibitors), and a tailored approach to drug management as evolving strategies for the more successful implementation of GDMT.

Statins, vascular calcification, and vitamin K-dependent proteins: Is there a relation?

The present cross-sectional clinical study aimed to examine the connection between statin exposure, coronary artery calcification (CAC), and vitamin K-dependent proteins (VKDPs) in patients with cardiovascular (CV) conditions. Two groups of patients were studied: patients with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were also split into statin users and non-users. The following VKDPs were measured in plasma: uncarboxylated Matrix Gla-protein (ucMGP), undercarboxylated (ucOC), and carboxylated osteocalcin (cOC), Gla-rich protein (GRP). CAC score (CACS) was determined by multislice computed tomography. Among all the participants in the study, CACS was more pronounced in statin users compared to non-users; the same was found also among the CVD patients and among the controls. While the levels of ucMGP and GRP did not differ between statin users and non-users, ucOC and ucOC/cOC were significantly elevated in statin users, indicating vitamin K deficiency. There was a positive correlation between the levels of ucOC and CACS in the entire population and in the group of statin users, but not in statin non-users. No association was found between ucMGP or GRP and CACS. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists (VKAs). Our results are in agreement with the existing evidence about positive association between statins and vascular calcification. They enlighten to a certain extent the possible mechanisms through which statins may enhance calcium accumulation in arterial wall, namely, by inhibition of vitamin K dependent proteins and functions involved in vascular protection.

Circulating proinflammatory peptides related to abdominal adiposity and cardiometabolic risk factors in healthy prepubertal children.

OBJECTIVES: To analyze the circulating levels of proinflammatory peptides in healthy prepubertal children in relation to abdominal obesity, measured by waist circumference (WC), and to investigate their interactions with cardiometabolic risk factors. DESIGN AND METHODS: A cross-sectional study of 137 healthy prepubertal children with a mean age of 8.0±0.1 years divided into three groups according to their WC as a measure of abdominal obesity: 'normal-WC' children (25th-75th percentile, n=48), 'children at risk' (75th-90th percentile, n=39), and 'abdominally obese' (≥90th percentile, n=50) children. Auxological measurements and blood pressure (BP) were taken. Fasting levels of high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL6), tumor necrosis factor-α (TNF-α), glucose, insulin, and lipid profile were measured. Insulin resistance (IR) was assessed by homeostasis model assessment of IR (HOMA-IR). RESULTS: Abdominally obese children had significantly higher BP, insulin, HOMA-IR, total cholesterol and triglycerides (TG) compared with their normal-WC counterparts (P<0.05). HsCRP concentrations increased proportionally with the degree of abdominal obesity (r=0.443, P<0.0001), whereas IL6 and TNF-α were not significantly associated with any of the adiposity variables. After controlling for adiposity, hsCRP was significantly correlated with systolic BP (r=0.257, P=0.004), TNF-α levels were related to high-density lipoprotein cholesterol (HDL-C; r=-0.216, P=0.016) and TG (r=0.196, P=0.029), whereas the relationship between IL6 and HDL-C reduced its magnitude to an insignificant level (r=-0.173, P=0.055). CONCLUSIONS: Healthy prepubertal children with abdominal obesity have associated inflammatory and cardiometabolic alterations, interacting with each other.

Waist circumference percentile curves for Bulgarian children and adolescents aged 6-18 years.

BACKGROUND: Waist circumference (WC) is a simple, easily available anthropometric measurement, giving relevant information about fat distribution and reflecting the degree of central adiposity in children. It appears to be the main risk factor for the progress of the metabolic syndrome. Our aim was to develop age- and sex-specific WC percentile curves for Bulgarian children/adolescents and to compare them with those from other countries. METHODS: A representative cross-sectional study of 3,810 healthy Bulgarian children/adolescents (2,052 males) aged 6-18 years, conducted in 2006/07. Body weight, height and WC were measured and body mass index (BMI) was calculated. Sex- and age-specific WC percentile curves were constructed using the LMS method. RESULTS: WC increased with age in both sexes (P<0.0001), with higher values in boys at every age and percentile point. This difference became significant from age 11 years onwards (P<0.05). The boys' values continued to increase steeply after this age, while in girls we found a constant continuing increase until the age of 15. Thereafter WC began to decrease and level off. The WC percentile values in Bulgarian children were lower than in US children, higher than in British and Turkish children, and similar to those of their Cypriot peers. CONCLUSIONS: For the first time, WC percentile curves were constructed for Bulgarian children/adolescents. A unique standardized method for WC measurement in children is needed for more acceptable international comparisons.