Appendix D: Definitions used in the guideline

Appendix D: Definitions used in the guideline

Adults with FH

For the purposes of this guideline, 'adults' includes all persons with familial hypercholesterolaemia (FH; heterozygous or homozygous) who are 16 years and older.

Cascade testing

Cascade testing is a mechanism for identifying people at risk of a genetic condition by a process of family tracing. For FH the test employed is measurement of low-density lipoprotein cholesterol (LDL-C) in the blood, and/or a DNA test if a disease-causing mutation has been identified in the index individual/proband (see below).

Children/young people

For the purposes of this guideline, 'children' refers to persons younger than 10 years; 'young people' refers to persons from 10 years of age up to the age of 15 years. The definitions used here are not prescriptive and healthcare professionals are expected to exercise their judgement and consider the wishes of the patients, and their families or carers when interpreting these terms in individual instances.

Child-focused setting

Child-focused refers to valuing the child's view and validating their voice in making decisions impacting their lives. A child-focused facility or space is one designed from the viewpoint of the service recipients.

Family history

The structure and relationships within the family that relates information about diseases in family members.

First-degree relative

A person's biological parents, brothers and sisters, and children.

Heterozygous FH

High LDL-C concentration in the blood caused by an inherited mutation from one parent only. People with FH are at increased risk of cardiovascular disease.

High-intensity statin

Statins are classified as high intensity if they produce greater LDL-C reductions than simvastatin 40 mg (for example, simvastatin 80 mg and appropriate doses of atorvastatin and rosuvastatin).

Homozygous FH

Very high LDL-C concentration in the blood caused by an inherited mutation from both parents. When a person inherits exactly the same affected gene from both parents this is called truly 'homozygous' FH. When the mutations in the LDL receptor gene (or equivalent) are different, this state is called 'compound heterozygous'. In general, the overall effect in both states is similar, in that LDL-C concentrations are very high. Both groups of patients have the same clinical pattern and high risk of cardiovascular disease.

For clinical purposes, both homozygous FH and compound heterozygous FH can be regarded as behaving in a similar manner. Therefore, for the purposes of this guideline the term 'homozygous FH' is used to also encompass compound heterozygous FH.

Index individual (synonymous with 'proband')

The original patient who is the starting point for follow-up of other members of a family when investigating for possible causative genetic factors of the presenting condition.

Lipid measurements/

These terms refer to the measurement of total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and LDL-C. LDL-C is not usually measured directly but calculated from the TC, TGs and HDL-C, ideally using a fasting sample.

Such tests are usually done in a clinical biochemistry laboratory.


An identified change in the DNA sequence of a gene that is predicted to damage the normal function of the gene and so cause disease.


A method of characterising the relatives of an index individual/case and their family relationship as well as problems or illnesses within the family. This information, often represented graphically as a family tree, facilitates analysis of inheritance patterns. Study of a trait or disease begins with the affected person (the index individual). The pedigree is drawn as the relatives are described. One begins with the siblings of the index individual and proceeds to the parents; relatives of the parents, including brothers, sisters, nephews, nieces, grandparents, and so on. At least three generations are usually included. Illnesses, hospitalisations, causes of death, miscarriages, abortions, congenital anomalies, and any other unusual features are recorded.

Premature coronary heart disease

For the purpose of this guideline, this refers to a coronary event that has occurred (1) before 55 years of age in a male index individual or 65 years of age in a female index individual, (2) before 60 years of age in a first-degree relative, or (3) before 50 years of age in a second-degree relative.


The affected (index) individual through whom a family with a genetic disorder is ascertained.

Second-degree relative

A person's biological grandparent, grandchild, uncle, aunt, niece, nephew, half sister or half brother.

Simon Broome register

A computerised research register of people with FH, based in Oxford. Research from this voluntary register has led to several publications describing the natural history of FH in the UK. The 'Simon Broome criteria' for diagnosis were based on a study of this group of people with FH.


One who has expertise in a particular field of medicine by virtue of additional training and experience. For this guideline, we use specialist to refer to a healthcare professional with an expertise in FH.

Specialist centre

The definition of a specialist centre is not rigid and is based on a combination of patient treatment services, numbers and ages of people attending there, the presence of a multi-disciplinary team (which may include, for example, physicians, lipidologists, specialist nurses and dietitians), the ability to manage the more unusual manifestations of the condition and the additional functions such as research, education and standard setting. Care is supervised by expert healthcare professionals but shared with local hospitals and primary care teams. Although details of the model may vary between patients and areas, the key is that specialist supervision oversees local provision with the patient seen at diagnosis for initial assessment and then at least annually for review.

Tendon xanthomata

A clinically detectable nodularity and/or thickening of the tendons caused by infiltration with lipid-laden histiocytes (macrophages in connective tissue).

A distinctive feature of FH that most frequently affects the Achilles tendons but can also involve tendons on the back of the hands, elbows and knees.

Third-degree relative

A person's biological great grandparent, great grandchild, great aunt, great uncle, first cousin, grand nephew or grand niece.

Urgent referral

For the purposes of this guideline, urgent referral is as soon as possible with a maximum of 14 days.

  • National Institute for Health and Care Excellence (NICE)