In general practice, patients with familial hypercholesterolaemia may appear as only having a single cardiovascular risk factor (that is, raised cholesterol or family history), and standard cardiovascular risk-assessment tools (for example, Framingham, QRISK®2) substantially underestimate their risk and must not be used. This is because these individuals are hypercholesterolaemic from infancy with a higher cholesterol-years burden,10
leading to a greatly increased risk of atherosclerosis, thus benefiting from early and aggressive lipid-lowering treatment to prevent premature CHD.
Despite being provided with thorough information and advice from specialists, patients may still not be clear about their condition and are likely to consult the GP and practice nurse. A recent survey suggested that although 90% of patients with familial hypercholesterolaemia knew about cholesterol and the reasons for treatment, only three-quarters knew that they were at risk of a cardiac event, with one-third knowing the mode of inheritance of familial hypercholesterolaemia and one-fifth being aware of their own family histories.11
Even while under specialist care, opportunistic contact with the primary care practitioner can provide an opportunity to monitor drug adherence, reinforce lifestyle advice (for example, smoking cessation), identify the presence of any new risk factors (for example, hypertension, and recent family history), investigate symptoms of coronary heart disease, and enquire about drug side-effects. If the patient has been discharged from specialist care, this assessment should be offered in general practice at least on an annual basis, with fasting lipid profile, renal function, and glucose testing arranged. Since there is a small possibility of fetal abnormality associated with statin use in early pregnancy,12
it is recommended that contraception should be discussed at the commencement of statin treatment in women of child-bearing age, and that this discussion is revisited regularly. Standard effective contraceptive methods, including the combined oral contraceptive, are not contraindicated for women with familial hypercholesterolaemia. However, because there is a potential small increased risk of cardiovascular events with the use of combined oral contraceptives, healthcare professionals should consider other forms of contraception. The evidence for safety of the combined oral contraceptives was derived from its use in women with non-familial hypercholesterolaemia, and indicates that primary and secondary generation combined oral contraceptives have a slightly higher myocardial infarction risk than third-generation oral contraceptives, for which myocardial infarction risk is negligible.13,14
Further, women planning to start a family should stop lipid-lowering treatment 3 months before attempting to conceive.
Referral back to a specialist with expertise in familial hypercholesterolaemia should be considered if the patient develops new CHD risk factors or drug side-effects, to instigate drug modification as part of pre-pregnancy planning, or in patients who do not achieve their target reduction in LDL, that is, a ≥50% reduction from baseline levels.15
It is not recommended that GPs should be responsible for cascade screening, but members of the extended family who are in the same practice should be referred to the specialist service, where screening will be coordinated. GPs should encourage index cases with familial hypercholesterolaemia to discuss screening with relatives, while relatives directly contacting clinicians should be offered referral. The Simon Broome criteria should not be used to make a diagnosis of familial hypercholesterolaemia in these relatives, as the LDL cut-offs in these criteria will miss relatives at risk of familial hypercholesterolaemia.9
GPs should have a low threshold for urgent cardiological referral if patients develop symptoms and/or signs of CHD. Further, all pregnant women with familial hypercholesterolaemia should be referred early to a shared care team comprising an experienced obstetrician and a cardiologist. Those women who do conceive while on statins should stop treatment immediately and be referred urgently to an obstetrician for fetal assessment. In pregnancy, routine serum cholesterol measurements are not recommended, as there are marked changes in lipids and lipoproteins in pregnancy.16
Breast feeding should be encouraged in familial hypercholesterolaemia as for the general population, but systemically absorbed lipid-lowering treatments (such as statins) should not be used until after weaning.
Familial hypercholesterolemia is a relatively common inherited condition of abnormal lipid metabolism that is associated with significant morbidity and mortality. This is effectively treated by the statin class of lipid-lowering drugs. Possible familial hypercholesterolaemia can be identified in general practice using routine patient information and investigations, and patients with confirmed familial hypercholesterolaemia warrant treatment with potent statins.