These recommendations are in line with a guideline published by the National Institute for Health and Clinical Excellence (NICE), Identification and management of familial hypercholesterolaemia [NICE, 2008], and a summary of NICE guidance published in the British Medical Journal, which helps to define the role of primary care [Wierzbicki et al, 2008].

• However, there is no clear guidance from NICE on the use in primary care of blood pressure lowering and antiplatelet medication specifically in people with familial hypercholesterolaemia (FH) [NICE, 2004; NICE, 2006; NICE, 2008].

Blood pressure

• Recommendations regarding the threshold for, and target of, blood pressure lowering medication are extrapolated from the guideline published by NICE, Hypertension: management of hypertension in adults in primary care (partial update of NICE clinical guideline 18), in which treatment with blood pressure lowering medication is recommended in 'patients at raised cardiovascular risk (10-year risk of CVD of 20% or more, or existing cardiovascular disease or target organ damage) with persistent blood pressure of more than 140/90 mmHg' [NICE, 2006]. This assumes that all people with FH are at raised cardiovascular risk.
• The recommendation to consider a higher threshold and a lower target in some cases is based on other evidence:
• Two other UK guidelines on the prevention of cardiovascular disease recommend that, for people with FH who are 40 years of age or younger, blood pressure lowering medication should only be started if blood pressure is consistently greater than 160/100 mmHg. Both guidelines also recommend that the target for all people being treated is a blood pressure less than 140/85 mmHg [British Cardiac Society et al, 2005; SIGN, 2007].
• Two recent, large cohort studies found that statins nearly normalize the coronary heart disease risk in people with FH [Neil et al, 2008; Versmissen et al, 2008].

Aspirin

• Recommendations regarding the use of aspirin are based on expert opinion expressed in two guidelines on the prevention of cardiovascular disease issued by the Joint British Societies (JBS) [British Cardiac Society et al, 2005] and the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2007]:
• Aspirin is recommended for adults with FH who are 40 years of age or more (by SIGN), but for those who are 50 years of age or more (by JBS). The lower age was selected by CKS on the basis that, untreated, people with FH are at very high risk of premature coronary heart disease [Marks et al, 2003].
• Recommendations to bring forward or delay the use of aspirin depending on statin use are based on comments from CKS external expert reviewers and the findings of two recent, large cohort studies that statins nearly normalize the coronary heart disease risk in people with FH [Neil et al, 2008; Versmissen et al, 2008] — see Statins versus placebo in adults. Furthermore, two recent randomized, controlled trials (not in people with FH) did not find that aspirin reduced the risk of most cardiovascular outcomes in some groups:
• The Women's Health Study, a primary prevention study involving 39,876 women 45 years of age or older (90% of whom were less than 65 years of age), found that aspirin 100 mg had no significant effect on the risk of fatal or non-fatal myocardial infarction compared with placebo (relative risk 1.02, 95% CI 0.84 to 1.25, p = 0.83), although aspirin significantly lowered the risk of stroke [Ridker et al, 2005].
• The prevention of progression of arterial disease and diabetes (POPADAD) trial found no statistically significant differences in the risk of any cardiovascular outcome between aspirin 100 mg and placebo in 1276 adults who were 40 years of age or more with type 1 or type 2 diabetes and asymptomatic peripheral arterial disease [Belch et al, 2008].
• The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial found that, compared with placebo, aspirin 81 mg or 100 mg did not reduce atherosclerotic events in 2539 Japanese adults with type 2 diabetes (hazard ratio 0.80, 95% CI 0.58 to 1.10, p = 0.16) [Ogawa et al, 2008].