15289-s-bos

48 | Chapter 4 Methods Study population Between February 2008 and June 2011 we included 145 consecutive patients with he-FH. Additionally, between November 2006 and January 2011 we included 131 consecutive patients with non-anginal chest pain (NACP) as a control group. Patients with NACP were used as a substitute for asymptomatic patients without he-FH because the radiation exposure limits the choice of controls to patients with an indication for cardiac computed tomography (CT). NACP patients were referred by their general practitioner for the evaluation of chest pain and underwent stress testing and cardiac CT. They did not have a history of coronary artery disease (CAD). NACP was defined as chest pain or discomfort that was not 1) provoked by exertion or emotional stress, or 2) relieved by rest or nitroglycerin(16). He-FH patients were recruited from our tertiary outpatient lipid clinic. He-FH was determined either by the presence of a confirmed LDLR or APO-B gene mutation (the patients did not have PCSK-9 mutations), or clinically as having a untreated LDL-C above the 95th percentile for gender and age in combination with at least one of the following: the presence of typical tendon xanthomas in the patient or a first degree relative; an LDL-cholesterol level above the 95th percentile for gender and age in a first degree relative; proven CAD in a first degree relative under the age of 60 (17). DNA samples were taken of all patients with a clinical suspicion of he-FH and were sent to a central laboratory for mutational screening (18). A complete overview of the mutations found and clinical characteristics of both LDLR-negative and LDLR-defective he-FH has been previously published (19). Plasma lipid levels were measured on fasting blood samples at time of inclusion. Cholesterol levels before statin treatment were obtained from patient medical records, and used as the variable maximum untreated total cholesterol, and untreated maximum LDL cholesterol (maxLDL). Exclusion criteria were: symptoms of CAD, history of CAD, rheumatic fever or known aortic valve pathology, although cardiac ultrasounds were not routinely performed prior to inclusion. Patients with a secondary cause of hypercholesterolemia such as renal, liver or thyroid disease were also excluded from the study. Further exclusion criteria were renal insufficiency (serum creatinine > 120 unmold/L), known contrast allergy and irregular heart rhythm (atrial fibrillation). In asymptomatic he-FH patients, the inclusion age was 40-70 years for men. Women were included after childbearing age (45-70 years) because of potential radiation-induced harm to the fetus or ovaries.