Population, genetic, and clinical studies demonstrated a causative and continuous, from other plasma lipoproteins independent relationship between elevated plasma lipoprotein (a) Lp(a) concentration ...and the development of cardiovascular disease (CVD), mainly those related to athe-rosclerotic CVD, and calcific aortic stenosis. Currently, a strong international consensus is still lacking regarding the single value which would be commonly used to define hyperlipoproteinemia (a). Its prevalence in the general population is estimated to be in the range of 10%-35% in accordance with the most commonly used threshold levels (>30 or >50 mg/dL). Since elevated Lp(a) can be of special importance in patients with some genetic disorders, as well as in individuals with otherwise controlled major risk factors, the identification and establishment of the proper therapeutic interventions that would lower Lp(a) levels and lead to CVD risk reduction could be very important. The majority of the classical lipid-lowering agents (statins, ezetimibe, and fibrates), as well as nutraceuticals (CoQ10 and garlic), appear to have no significant effect on its plasma levels, whereas for the drugs with the demonstrated Lp(a)-lowering effects (aspirin, niacin, and estrogens), their clinical efficacy in reducing cardiovascular (CV) events has not been unequivocally proven yet. Both Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors can reduce the plasma Lp(a) by approximately 20%-30% on average, in parallel with much larger reduction of low-density lipoprotein cholesterol (up to 70%), what puts us in a difficulty to conclude about the true contribution of lowered Lp(a) to the reduction of CV events. The most recent advancement in the field is the introduction of the novel apolipoprotein (a) apo(a) antisense oligonucleotide therapy targeting apo(a), which has already proven itself as being very effective in decreasing plasma Lp(a) (by even >90%), but should be further tested in clinical trials. The aim of this review was to present some of the most important accessible scientific data, as well as dilemmas related to the currently and potentially in the near future more widely available therapeutic options for the management of hyperlipoproteinemia (a).
Aims
To determine whether the Joint European Societies guidelines on cardiovascular prevention are being followed in everyday clinical practice of secondary prevention and to describe the lifestyle, ...risk factor and therapeutic management of coronary patients across Europe.
Methods and results
EUROASPIRE IV was a cross-sectional study undertaken at 78 centres from 24 European countries. Patients <80 years with coronary disease who had coronary artery bypass graft, percutaneous coronary intervention or an acute coronary syndrome were identified from hospital records and interviewed and examined ≥ 6 months later. A total of 16,426 medical records were reviewed and 7998 patients (24.4% females) interviewed. At interview, 16.0% of patients smoked cigarettes, and 48.6% of those smoking at the time of the event were persistent smokers. Little or no physical activity was reported by 59.9%; 37.6% were obese (BMI ≥ 30 kg/m2) and 58.2% centrally obese (waist circumference ≥ 102 cm in men or ≥88 cm in women); 42.7% had blood pressure ≥ 140/90 mmHg (≥140/80 in people with diabetes); 80.5% had low-density lipoprotein cholesterol ≥ 1.8 mmol/l and 26.8% reported having diabetes. Cardioprotective medication was: anti-platelets 93.8%; beta-blockers 82.6%; angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 75.1%; and statins 85.7%. Of the patients 50.7% were advised to participate in a cardiac rehabilitation programme and 81.3% of those advised attended at least one-half of the sessions.
Conclusion
A large majority of coronary patients do not achieve the guideline standards for secondary prevention with high prevalences of persistent smoking, unhealthy diets, physical inactivity and consequently most patients are overweight or obese with a high prevalence of diabetes. Risk factor control is inadequate despite high reported use of medications and there are large variations in secondary prevention practice between centres. Less than one-half of the coronary patients access cardiac prevention and rehabilitation programmes. All coronary and vascular patients require a modern preventive cardiology programme, appropriately adapted to medical and cultural settings in each country, to achieve healthier lifestyles, better risk factor control and adherence with cardioprotective medications.
Familial hypercholesterolemia (FH) is arguably the most common monogenic disorder in humans, but severely under-diagnosed. Individuals with untreated FH have an over 10-fold elevated risk of ...cardiovascular complications as compared to unaffected individuals; early diagnosis and timely management substantially reduce this risk.
Slovenia has gradually implemented the program of universal FH screening in pre-school children, consisting of a two step approach: (1) universal hypercholesterolemia screening in pre-school children at the primary care level; (2) genetic FH screening in children referred to the tertiary care level according to clinical guidelines (with additional cascade screening of family members). The program is presented in detail.
We analyzed retrospective data (2012–2016), to assess the efficiency of the universal FH screening program. In that period, 280 children (59.3% female) were referred to our center through the program for having TC > 6 mmol/L (231.7 mg/dL) or >5 mmol/L (193.1 mg/dL), with a positive family history of premature cardiovascular complications at the universal hypercholesterolemia screening.
170 (57.1% female) of them were fully genotyped, 44.7% had an FH disease-causing variant (28.8% in LDLR gene, 15.9% in APOB, none in PCSK9), one patient was LIPA positive, and 40.9% of the remaining patients carried an ApoE4 isoform; genetic analysis is still ongoing for one-third of the referred patients. For almost every child with confirmed FH, one parent had highly probable FH.
FH was confirmed in almost half of the referred children, detected through the universal screening for hypercholesterolemia.
•FH is a common monogenic disorder but severely under diagnosed and under treated.•FH screening in childhood with early treatment is needed.•Slovenia has a unique and effective program of universal FH screening in children.•Almost half of the children referred through the program had FH causing mutation.
Abstract
In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, ...nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.
Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is ...modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), “lower is better for longer”, and the recent data have strongly emphasized the need of also “the earlier the better”. In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual’s calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an ‘Extremely High Risk’ group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.
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Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There ...are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies-PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib-for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group.
The scientific discourse on vegan diets for children and adolescents primarily involves referencing position statement papers from different scientific and professional organizations, including ...paediatric associations. Over the past two decades, specialized associations have issued official statements and published position papers about adopting well-designed vegan diets during crucial life stages, including pregnancy and lactation, infancy, and childhood. A subset of these associations firmly supports the notion that a well-designed vegan diet can indeed be healthy and support normal growth and development during particularly delicate life stages, emphasizing careful planning, vitamin B12 supplementation, and regular supervised medical and dietetics oversight. In contrast, specific paediatric associations caution against vegan diets for children and adolescents, citing potential harm and the lack of adequate substantiation. These criticisms in position papers frequently point to lower-quality studies and/or outdated studies. Additionally, concerns extend to comparing vegan and omnivorous diets, considering public health issues such as obesity and early stages of cardiovascular disease as well as the risk of prediabetes and type 2 diabetes. Notably, some scepticism stems from studies where children’s adherence to a well-designed vegan diet is incomplete. Scientific rigor suggests performing a comparable assessment of omnivorous and vegan diets. This narrative review highlights the need for a comprehensive, up-to-date literature review to inform balanced perspectives on vegan diets for children and adolescents. Researchers and decision-makers should aim to actively improve the design and consistent implementation of both diet types.
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