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TC .290 mg/dL or LDLc .190 mg/dL + familial history of TX presence

TC .290 mg/dL or LDLc .190 mg/dL + familial history of myocardial

infarction or family history of hypercholesterolemia

Age ,20 yo, TC .270 mg/dL

Age 20–29 yo, TC .290 mg/dL

Age 30–39 yo, TC .340 mg/dL

Age $40 yo, TC .360 mg/dL


1 (score)

Premature vascular disease


TX and/or arcus cornealis


Children ,18 yo with LDLc .95th percentile


Premature vascular disease


TX presence


Arcus cornealis (,45 yo)


$330 mg/dL


250–329 mg/dL


190–249 mg/dL


155–189 mg/dL


Notes: aClinical criteria proposed for genetic testing.100 Abbreviations: SBRG, Simon Broom Register Group from United Kingdom;18 MeDPeD, Make early Diagnosis to Prevent early Death program in the United States;98 DLCN MEDPED: Dutch Lipid Clinic Network MEDPED group criteria scoring system for the diagnosis of heterozygous FH patients (“Definitive” diagnosis .7 points, “Probable” 5–7 points).99

De Castro-Orós et al

Table 4 Familial hypercholesterolemia diagnostic criteria

SBRG Definitive Possible


Civeira et ala


Family with clinical suspicions of FH


Familial history

Personal history Physical exam

LDLc levels

Familal history of TX + LDLc $190 mg/dL Nonfamily history of TX

Age ,30 yo with LDLc .220 mg/dL Age 30–39 yo with LDLc .225 mg/dL Age .40 yo with LDLc .235 mg/dL

diagnostic guidelines published by our group, we recommend genetic analysis because these populations use to present a few LDLR mutations that are responsible for most FH cases; the most frequent causative mutations are known; or in subjects from families with known mutations with an uncertain clinical diagnosis (Table 4).19 We have recently published a study that proves the molecular diagnosis usefulness to distinguish familial combined hyperlipidemia (FCH) of FH patients, when clinical presentation can produce a misclassification, which can be solved by finding LDLR mutations that cause the disease.104 At this work, 28 carriers of LDLR mutations were found in 143 unrelated FCH subjects. Our group has recently shown that presence of TX is highly specific of FH when primary hypercholesterolemia, family history of hypercholesterolemia, and premature coronary disease are presented. Moreover, a sonographic evaluation of Achilles tendons for the diagnosis of FH has been performed.105 Thus, taking all these findings together, a new set criteria to maximize the likelihood of genetic confirmation in subjects with clinical suspicions of FH based on age, TX presence, and LDLc levels have been proposed (Table 4).100


The standard of care for patients with homozygous FH has been LDL apheresis.106,107 The LDLc reduction observed with

LDL apheresis is over 60%, and similar values were observed in Lp(a). LDL apheresis is an invasive and expensive but safe procedure. The inconvenience of this method is that it has to be performed at 1-weekly or 2-weekly intervals.108

A statin is the drug of first choice in the majority of cases. The safety and efficacy of statins as LDLc lowering drugs and their demonstrated performance in preventing CVD morbidity and mortality in primary and secondary prevention trials have been amply demonstrated. In addition, statins can be safely combined with either resins or ezetimibe. Furthermore, the LDLc-lowering effect of these drugs is not modified by the concomitant use of plant sterols/stanols that can be recommended also to these patients.109

Considering that ,100 mg/dL (2.6 mmol/L) is the optimal LDLc concentration defined byATPIII guidelines,26 it would be necessary to achieve mean reductions between 50% and 75% to reach that goal. Based on published data from both heFH and other high risk populations, three different LDLc goals can be recommended for heFH (Table 5). An important aspect of FH treatment with many benefits beyond LDLc lowering is a healthy lifestyle, which includes a healthy diet, ideal body weight, no smoking, and moderate physical activity. Although LDLc is the main CVD risk factor in FH patients, other risk factors such as smoking habit or low HDLc concentration are great modifiers of the CVD development.110


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The Application of Clinical Genetics 2010:3

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