Family History and Cardiovascular Risk in Familial Hypercholesterolemia

Abstract

Background-Elevated LDL cholesterol (LDL-C) levels in childhood predict cardiovascular disease (CVD) later in life.Familial hypercholesterolemia (FH) represents the paradigm of this relation. Methods and Results-The objectives of this study were to (1) establish the LDL-C level that provides the most accurate diagnosis of FH in children from families with known FH and (2) assess whether lipoprotein variation in these children is associated with premature CVD in relatives. Foremost, however, it was our objective to identify children with FH who are at high risk and in need of early intervention. A total of 1034 consecutive children from FH kindreds were investigated. First, LDL-C levels Ͼ3.50 mmol/L had a 0.98 post-test probability (95% CI, 0.96 to 0.99) of predicting the presence of an LDL receptor mutation. Second, children with FH in the highest LDL-C tertile (Ͼ6.23 mmol/L) had a 1.7-times higher incidence (95% CI, 1.24 to 2.36) of having a parent with FH suffering from premature CVD (Pϭ0.001). In addition, such a parent was found 1.8 times more often (95% CI, 1.20 to 2.59) among children with FH who had HDL-C Ͻ1.00 mmol/L (Pϭ0.004). Last, children with FH whose lipoprotein(a) was Ͼ300 mg/L had a 1.45-times higher incidence (95% CI, 0.99 to 2.13) of having a parent with FH suffering from premature CVD (Pϭ0.05). Conclusions-In FH families, LDL-C levels allow accurate diagnosis of FH in childhood. Moreover, increased LDL-C and lipoprotein(a) and decreased HDL-C levels in children identify FH kindreds with the highest CVD risk. (Circulation.

Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation

“…Boys and girls with potential heterozygous FH should also be screened before the age of 10 years, preferably between ages of 5 and 10 years. However, earlier screening may be justified with a family history of CHD prior to age 55 years, especially in first-degree relatives [63,67,68], or at the specific request of parents wishing to embed healthy lifestyle measures at a very early age. Detection of FH in childhood employing three strategies can be considered: cascade screening, universal screening, or selective screening based on family history [21,27,66].…”

“…Plasma LDL-cholesterol level alone has excellent discrimination between those with and without FH below the age of 10 years [67,70,71]. However, because of biological variation [29,72], the average of at least two fasting LDL-cholesterol levels should be used to make the diagnosis of FH [19,20,65].…”

Management of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization

“…Sometimes LDL-C levels below 4 mmol/L (160 mg/dL) are encountered in children who carry mutations on the LDL receptor or apolipoprotein B (ApoB) genes. In The Netherlands, Wiegman and colleagues [29], after studying 1034 children from families with FH (confirmed by genetic testing), noted that a fasting LDL-C level of 3.5 mmol/L (135 mg/dL) predicted the presence of FH with a posttest probability of 0.98 for differentiating affected children from non-affected children. As in most epidemiological studies of Belgian children, the levels of TC (LDL-C was not measured in these studies) were quite similar to those of Wiegman et al in the Dutch non-FH children.…”

Necessidades básicas insatisfeitas, desnutrição infantil e risco de doenças na vida

“…O estresse psicológico e a estigmatização social produzidos por esses distúrbios nutricionais são tão graves quanto a sua morbidade. O excesso de peso se soma, em alguns casos, à dislipidemia e à hipertensão arterial como fatores de risco para o aparecimento de eventos cardiovasculares (8,9) . O estudo Bogalusa, efetuado pela Academia Americana de Pediatria em 1999, demonstrou que, em crianças com sobrepeso e obesidade, o colesterol total foi 2,4 a 7,1 vezes mais elevados, o LDL colesterol foi 12,6 vezes mais elevado, sendo o LDL (low density liprotein) colesterol e o IMC os fatores mais fortemente relacionados ao aumento de espessura da camada íntima arterial (10,11) .…”