The German CaRe high registry for familial hypercholesterolemia - Sex differences, treatment strategies, and target value attainment.

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

Lipid Profile and Lipoprotein(a) Testing.

BACKGROUND: The treatment of dyslipidemias plays a major role in the primary and secondary prevention of cardiovascular disease. Proper evaluation of the patient's lipid status is very important for risk assessment and as a guide to treatment. METHODS: This review is based on publications retrieved by a selective search of the literature, including current guidelines. RESULTS: Measurement of the plasma concentration of cholesterol, triglycerides, HDL- and LDL-cholesterol, calculation of the non-HDL cholesterol concentration, and-on a single occasion-determination of the lipoprotein (a) concentration enable the clinician to quantify the lipid-associated health risk and monitor the effects of treatment. These blood tests can be performed in a non-fasting state except in special situations (particularly, hypertriglyceridemia). The HDL quotient is an obsolete measure. The main goal of treatment is to achieve an LDL-cholesterol level adequate to the patient's cardiovascular risk through lifestyle modification and, if necessary, medication. A high lipoprotein (a) concentration cannot be lowered with orally administered drugs; above all, patients should lower their LDL-cholesterol levels while minimizing all other risk factors. CONCLUSION: Measurement of the concentration of cholesterol, triglycerides, and HDL- and LDL-cholesterol and calculation of the non-HDL-C suffice as a guide to lipid-lowering treatment. The primary therapeutic goal is to lower LDL cholesterol.

Effects of age on non-communicable disease risk factors among Nepalese adults.

The growing burden of non-communicable diseases (NCDs) and an increase in the prevalence of the underlying risk factors are creating a challenge to health systems in low- and middle-income countries (LMICs). In Nepal, deaths attributable to NCDs have been increasing, as has life expectancy. This poses questions with regards to how age and various risk factors interact in affecting NCDs. We analyzed the effects of age on NCD risk factors, using data from the Nepalese STEPs survey 2019, a nationally representative cross-sectional study. Six sociodemographic determinants, four behavioral risk factors, and four biological risk factors were examined. Age effects were analyzed among three age groups: below 35 years (young), 35-59 years (middle aged) and 60 years and above (elderly). The prevalence of selected behavioral risk factors for NCDs, notably smoking, alcohol consumption and insufficient physical activity, and some biological risk factors (hypertension, hyperlipidemia) increases with age. The prevalence of most behavioral risk factors was highest among men and women aged 60 years and above. The prevalence of hypertension and hyperlipidemia was highest among the elderly, but the prevalence of diabetes and overweight/obesity was highest among the middle aged for both sexes. Age interactions in the association between behaviors and biological risk factors were surprisingly weak. However, age interactions were significant in the association between alcohol consumption and -hypertension, -overweight/obesity and -hyperlipidemia among women. While the prevalence of NCD risk factors tends to be higher among elders, the interaction between age and risk factors is complex. Most NCD risk factors are related to behaviors, which originate in young adulthood. It is necessary to diagnose and treat biological risk factors, in younger age groups before they manifest as NCDs. Similarly, behavior change interventions need to target these younger age groups to reduce the risk of NCDs later in life.

[Update lipidology : Evidence-based treatment of dyslipidemia]. / Update Lipidologie : Evidenzbasierte Behandlung von Fettstoffwechselstörungen.

The treatment of elevated plasma lipid levels plays an important role in prevention of atherosclerosis. Lowering of low-density lipoprotein (LDL) cholesterol with statins and if required with additional ezetimibe, bempedoic acid and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is of utmost importance. While lifestyle modification can strongly influence the cardiovascular risk, it only plays a minor role in lowering LDL cholesterol values. The overall (absolute) cardiovascular risk determines if and in what intensity lipid-lowering treatment should be implemented. Based on new results from interventional studies the LDL cholesterol target values have been reduced in recent years. Thus, in patients with a very high risk (for example patients with established atherosclerotic disease) an LDL cholesterol level of < 55 mg/dl (< 1.4 mmol/l, conversion mg/dl×0.02586=mmol/l) and at least a 50% reduction from baseline should be strived for. With respect to elevated triglyceride levels, either alone or simultaneously with elevated LDL cholesterol levels, the treatment goals are less clearly defined, despite the fact that elevated triglyceride levels are causally linked to atherosclerotic events. Lifestyle modifications can significantly reduce triglyceride levels and are often more effective than specific triglyceride-lowering medications, such as fibrates and omega­3 fatty acids. New lipid-lowering drugs for the treatment of patients with severely elevated triglyceride levels and elevated lipoprotein(a) levels are being developed but their clinical benefits still have to be confirmed in endpoint studies.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

Frequent questions and responses on the 2022 lipoprotein(a) consensus statement of the European Atherosclerosis Society.

In 2022, the European Atherosclerosis Society (EAS) published a new consensus statement on lipoprotein(a) [Lp(a)], summarizing current knowledge about its causal association with atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. One of the novelties of this statement is a new risk calculator showing how Lp(a) influences lifetime risk for ASCVD and that global risk may be underestimated substantially in individuals with high or very high Lp(a) concentration. The statement also provides practical advice on how knowledge about Lp(a) concentration can be used to modulate risk factor management, given that specific and highly effective mRNA-targeted Lp(a)-lowering therapies are still in clinical development. This advice counters the attitude: "Why should I measure Lp(a) if I can't lower it?". Subsequent to publication, questions have arisen relating to how the recommendations of this statement impact everyday clinical practice and ASCVD management. This review addresses 30 of the most frequently asked questions about Lp(a) epidemiology, its contribution to cardiovascular risk, Lp(a) measurement, risk factor management and existing therapeutic options.

Two years of pegvaliase in Germany: Experiences and best practice recommendations.

BACKGROUND: In 2019, pegvaliase was approved in Europe for the treatment of phenylketonuria (PKU) in patients aged 16 years and older with blood phenylalanine (Phe) concentrations above 600 µmol/L despite prior management with available treatment options. Since its European approval, German metabolic centres have gained valuable experience, which may be of benefit to other treatment centres managing patients on pegvaliase. METHODS: After a virtual meeting that was attended by nine German physicians, three German dietitians and one American physician, a follow-up discussion was held via an online platform to develop a set of recommendations on the use of pegvaliase in Germany. Eight German physicians contributed to the follow-up discussion and subsequent consensus voting, using a modified Delphi technique. The recommendations were supported by literature and retrospectively collected patient data. RESULTS: Consensus (≥75% agreement) was achieved on 25 recommendations, covering seven topics deemed relevant by the expert panel when considering pegvaliase an option for the treatment of patients with PKU. In addition to the recommendations, a retrospective chart review was conducted in seven of the centres and included 71 patients who initiated treatment with pegvaliase. Twenty-seven patients had been treated for at least 24 months and 23 (85.2%) had achieved blood Phe ≤600 µmol/L with some degree of diet normalisation. Of these patients, 14 had physiological blood Phe on a normalised diet. CONCLUSION: The practical consensus recommendations provide guidance on the different steps along the pegvaliase journey from clinical site requirements to treatment goals and outcomes. The recommendations are intended to support less experienced European metabolic centres with the implementation of pegvaliase, emphasising that a core treatment team consisting of at least a dietitian and metabolic physician is sufficient to initiate pegvaliase and support patients during their treatment journey.