Results:

In the study cohort of 821 FH lipid clinic patients on optimal or maximum tolerated lipid-lowering therapy, 102 or 12% of patients developed CV disease (CVD). Non-modifiable risk factors associated with a higher incidence of CVD event were a personal history of previous cardiac event (32 vs. 9%, p < 0.001) and a family history of CVD (58 vs. 40%, p = 0.001). Modifiable risk factors associated with a higher incidence of CVD event included hypertension (70 vs. 22%, p < 0.001), smoking (32 vs. 14%, p < 0.001), higher on-treatment low-density lipoprotein (LDL) (162 +/- 54 vs. 135 +/- 58 mg/dL, p < 0.001), and lower on-treatment high-density lipoprotein (HDL) (50 +/-15 vs. 54+/- 15 mg/dL, p < 0.001). Of the patients who had a CV event on lipid-lowering therapy, 30% had subsequent CV event; this was strongly associated with current smokers. In this cohort of patients, current smokers had a four-time greater risk of CV events, and patients with poorly controlled hypertension (defined as two or more blood pressures >140/90) had a three-times greater risk. In this population treated in a lipid specialty clinic, it is also important to note that only 19% reached an LDL cholesterol level of <100, leading to a higher risk of CV events. Use of PCSK9 inhibitors, given studies that show both a reduction in LDL cholesterol and reduction in CV events, may be appropriate in this high-risk group of patients for whom maximum tolerated lipid-lowering therapy has been insufficient.