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32 | Chapter 3 Abstract Background and aims Statins reduce subclinical atherosclerosis and premature atherosclerotic cardiovascular disease (ASCVD) in patients with familial hypercholesterolemia (FH). However, some FH patients still develop ASCVD despite statin therapy. We compared subclinical atherosclerosis assessed by carotid plaque presence and intima media thickness (C-IMT), in long-term statin-treated FH patients to healthy controls. Furthermore we analysedwhether carotid ultrasonography findings associatedwith subclinical coronary atherosclerosis. Methods and results We assessed the presence of carotid plaques and C-IMT in 221 asymptomatic heterozygous FH patients (48% men; 46±15 years) on long-term (10.0±7.8 years) statin treatment and 103 controls (32% men, 47±16 years). The frequency of carotid plaques and C-IMT did not differ significantly between the FH patients and controls (69 (31%) versus 24 (23%), p=0.1 and 0.58±0.13 versus 0.58±0.12 mm, p=0.9, respectively). In a subgroup of 49 FH patients who underwent cardiac computed tomography, coronary artery calcification correlated with carotid plaque presence (R=0.47; p=0.001), but not with C-IMT (R=0.20; p=0.2). Conclusions Carotidplaques andC-IMT didnot differ between long-termstatin-treatedheterozygous FH patients and healthy controls. This shows that long-term statin treatment in these FH patients reduces carotid atherosclerosis to a degree of a healthy population. These findings strongly suggests that sonography of the carotid arteries during follow-up of statin-treated FH patients has limited value. Keywords • Carotid plaque presence • Carotid intima media thickness • Familial hypercholesterolemia • Residual risk