Clinical familial hypercholesterolemia - factors influencing diagnosis and cardiovascular risk in the general population

Background: Individuals with familial hypercholesterolemia (FH) are at high risk of developing cardiovascular disease due to high LDL cholesterol concentrations. Other cardiovascular risk factors may add to this risk. Methods: We used Dutch Lipid Clinic Network (DLCN) criteria to diagnose FH in 106,865 individuals from the Copenhagen General Population Study. The importance of cardiovascular risk factors on i) assignment to DLCN FH-categories; ii) risk of myocardial infarction (MI) within each DLCN FH-category; and iii) the absolute ten-year risk of atherosclerotic cardiovascular disease (ASCVD) in DLCN FH-categories was investigated. Results: Risk of being diagnosed with possible or probable FH was higher in individuals who smoked, had hypertension, a body mass index (BMI)≥30kg/m², triglycerides≥2mmol/L, and lipoprotein(a)>50mg/dL compared to individuals without the risk factor (all p < 0.04). Risk of MI was higher in possible FH if individuals were men (odds ratio: 8.95; 95 % confidence interval: 7.67–10.4), smoked (5.97 [4.90–7.28]), had hypertension (8.22 [7.04–9.59]), diabetes (9.11 [6.94–12.0]), or lipoprotein(a) levels>50mg/dL(5.05 [4.15–6.14]). Ten-year risk of ASCVD stratified by FH-category was stepwise higher in individuals who smoked, had diabetes, and had higher blood pressure. Highest risks of ASCVD were 58.4 % and 77 % in women and men, respectively, above age 55 years, who smoked, had diabetes, a systolic blood pressure of 160–179 mmHg, and a probable/definite FH diagnosis. Conclusion: The likelihood of being diagnosed with FH by the DLCN criteria was influenced by smoking, hypertension, BMI, and triglyceride and lipoprotein(a) concentrations in the general population. For individuals within the same possible or probable FH-category, age, male sex, smoking, hypertension, and diabetes independently added to the risk of MI and ASCVD.