Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.

BACKGROUND: Heterozygous familial hypercholesterolemia (FH) represents the most frequent monogenic disorder with an estimated prevalence of 1:250 in the general population. Diagnosis during childhood enables early initiation of preventive measures, reducing the risk of severe consecutive atherosclerotic manifestations. Nevertheless, population-based screening programs for FH are scarce. METHODS: In the VRONI study, children aged 5-14 years in Bavaria are invited to participate in an FH screening program during regular pediatric visits. The screening is based on low-density lipoprotein cholesterol measurements from capillary blood. If exceeding 130 mg/dl (3.34 mmol/l), i.e. the expected 95th percentile in this age group, subsequent molecular genetic analysis for FH is performed. Children with FH pathogenic variants enter a registry and are treated by specialized pediatricians. Furthermore, qualified training centers offer FH-focused training courses to affected families. For first-degree relatives, reverse cascade screening is recommended to identify and treat affected family members. RESULTS: Implementation of VRONI required intensive prearrangements for addressing ethical, educational, data safety, legal and organizational aspects, which will be outlined in this article. Recruitment started in early 2021, within the first months, more than 380 pediatricians screened over 5200 children. Approximately 50 000 children are expected to be enrolled in the VRONI study until 2024. CONCLUSIONS: VRONI aims to test the feasibility of a population-based screening for FH in children in Bavaria, intending to set the stage for a nationwide FH screening infrastructure. Furthermore, we aim to validate genetic variants of unclear significance, detect novel causative mutations and contribute to polygenic risk indices (DRKS00022140; August 2020).

Population-based screening in children for early diagnosis and treatment of familial hypercholesterolemia: design of the VRONI study.

Familial hypercholesterolemia (FH) is the most frequent monogenic disorder (prevalence 1:250) in the general population. Early diagnosis during childhood enables pre-emptive treatment, thus reducing the risk of severe atherosclerotic manifestations later in life. Nonetheless, FH screening programs are scarce. VRONI offers all children aged 5-14 years in Bavaria a FH screening in the context of regular pediatric visits. LDL-cholesterol (LDL-C) is measured centrally, followed by genetic analysis for FH if exceeding the age-specific 95th percentile (130 mg/dl, 3.34 mmol/l). Children with FH pathogenic variants are treated by specialized pediatricians and offered a FH-focused training course by a qualified training center. Reverse cascade screening is recommended for all first-degree relatives. VRONI aims to prove the feasibility of a population-based FH screening in children and to lay the foundation for a nationwide screening program.

Mid-Term Vascular Safety of Renal Denervation Assessed by Follow-up MR Imaging.

BACKGROUND/AIMS: Renal denervation (RDN) emerged as a treatment option for reducing blood pressure (BP) in patients with treatment-resistant hypertension (TRH). However, concerns have been raised regarding the incidence of late renal artery stenosis or thromboembolism after RDN. The goal of the current study was, therefore, to conduct a prospective clinical trial on the mid-term vascular integrity of the renal arteries and the perfusion of the renal parenchyma assessed by magnetic resonance imaging (MRI) in the follow-up after catheter-based RDN. METHODS: In our single-centre investigator initiated study, 51 patients with true TRH underwent catheter-based RDN using the Symplicity Flex(TM) catheter (Medtronic Inc., Palo Alto, CA). Follow-up MRI was performed at a median of 11 months (interquartile range 6-18 months) after RDN on a 1.5T MR unit. High-resolution MR angiography (MRA) and MRI results were compared to the baseline digital angiography of renal arteries obtained at time of RDN. In case of uncertainties (N = 2) catheter angiography was repeated. RESULTS: Both office and 24-h ambulatory BP were significantly reduced 6 and 12 months after RDN. Renal function remained unchanged 6 and 12 months after RDN. In all patients, MRA excluded new or progression of pre-existing low grade renal artery stenosis as well as focal aneurysms at the sites of radiofrequency ablation. In none of the patients new segmental perfusion deficits in either kidney were detected on MRI. CONCLUSIONS: No vascular or parenchymal complications after radiofrequency-based RDN were detected in 51 patients followed up by MRI.