Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score ≥6. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy.

Coronary heart disease (CHD) is the main cause of death and morbidity in the world. There is a strong evidence that the atherosclerotic process begins in childhood and that hypercholesterolaemia is a CHD major risk factor. Hypercholesterolaemia is a modifiable CHD risk factor and there is a tracking of hypercholesterolaemia from birth to adulthood. Familial hypercholesterolaemia (FH) is the most common primitive cause of hypercholesterolaemia, affecting 1:200–250 individuals. Early detection and treatment of hypercholesterolaemia in childhood can literally “save decades of life”, as stated in the European Atherosclerosis Society Consensus. Multiple screening strategies have been proposed. In 2008, the American Academy of Pediatrics published the criteria for targeted screening, while some expert panels recommend universal screening particularly in the young, although cost effectiveness has not been fully analysed. Blood lipid profile evaluation [total cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), High-Density Lipoprotein Cholesterol (HDL-C) and triglycerides] is the first step. It has to be ideally performed between two and ten years of age. Hypercholesterolaemia has to be confirmed with a second sample and followed by the detection of family history for premature (before 55 years in men and 60 years in women) or subsequent cardio-vascular events and/or hypercholesterolaemia in 1st and 2nd degree relatives. The management of hypercholesterolaemia in childhood primarily involves healthy lifestyle and a prudent low-fat diet, emphasising the benefits of the Mediterranean diet. Statins are the cornerstone of the drug therapy approved in USA and in Europe for use in children. Ezetimibe or bile acid sequestrants may be required to attain LDL-C goal in some patients. Early identification of children with severe hypercholesterolaemia or with FH is important to prevent atherosclerosis at the earliest stage of development, when maximum benefit can still be obtained via lifestyle adaptations and therapy. The purpose of our review is to highlight the importance of prevention and treatment of hypercholesterolaemia starting from the earliest stages of life.

Coronary Heart Disease (CHD) is a major mortality and morbidity cause in adulthood worldwide. The atherosclerotic process starts even before birth, progresses through childhood and, if not stopped, eventually leads to CHD. Therefore, it is important to start prevention from the earliest stages of life. CHD prevention can be performed at different interventional stages: primordial prevention is aimed at preventing risk factors, primary prevention is aimed at early identification and treatment of risk factors, secondary prevention is aimed at reducing the risk of further events in those patients who have already experienced a CHD event. In this context, CHD risk stratification is of utmost importance, in order to tailor the preventive and therapeutic approach. Nutritional intervention is the milestone treatment in pediatric patients at increased CHD risk. According to the Developmental Origin of Health and Disease theory, the origins of lifestyle-related disease is formed in the so called “first thousand days” from conception, when an insult, either positive or negative, can cause life-lasting consequences. Nutrition is a positive epigenetic factor: an adequate nutritional intervention in a developmental critical period can change the outcome from childhood into adulthood.

Familial hypercholesterolaemia (FH) is a common genetic disorder characterized by lifelong elevated LDL cholesterol (LDL-C) concentrations. FH exists in two forms: heterozygous FH (HeFH), which affects around 1 in 300 people worldwide, and homozygous FH (HoFH), which affects around 1 in 300 000. Individuals with FH are at increased risk of premature atherosclerotic cardiovascular disease (ASCVD) and death, and those with HoFH are, if untreated, at extreme risk of ASCVD manifestations even before adulthood. Early diagnosis and treatment in childhood can extend or normalize life expectancy, but limited awareness, underdiagnosis, and undertreatment remain major challenges. This consensus statement aims to address these challenges, supported by increased knowledge of the pathogenesis of FH and the availability of an increasing range of lipid-lowering therapies (LLTs) that can be used from early ages. To increase the detection rate of FH, all countries are encouraged to establish a paediatric screening programme and, given that current diagnostic criteria often fail to identify children with an FH-causing genetic variant, revised diagnostic criteria are presented. Updated LDL-C treatment goals are proposed, and the importance of starting LLTs before puberty in children with HeFH, and, if needed, from 6 years, is highlighted. Guidance on how to manage FH is provided, including treatment algorithms for use in children with either HeFH or HoFH and a discussion on how to promote a smooth transition to adult care. Early detection and optimal treatment as advocated in this consensus statement are crucial to improving life expectancy for children and adolescents with FH.