Initiation of PCSK9 inhibition in patients with heterozygous familial hypercholesterolaemia entering adulthood: a new design for living with a high-risk condition?

Abstract

According to current estimates, as many as 4.5 million people in Europe suffer from the heterozygous form of familial hypercholesterolemia (HeFH).1 Their plasma concentration of low-density lipoprotein cholesterol (LDL-C) is two to three times above normal from birth, and accordingly, if untreated, the risk of coronary heart disease (CHD) and acute myocardial infarction (AMI) is markedly increased compared with non-HeFH populations.1 Indeed, in the pre-statin era, a clinical study on the incidence of CHD in patients with molecularly defined HeFH showed that the mean age of onset of symptomatic CHD was 42 ± 7 (SD) years for men and 48 ± 11 years for women, and that the corresponding ages at the time of first AMI were 47 ± 12 and 59 ± 13 years, respectively ( Figure 1 ).2 The early onset of clinically significant CHD in the pre-statin era is understandable, since the plasma concentration of LDL-C strongly elevated from birth. It also explains the early onset of subclinical coronary atherosclerosis in these patients. Thus, extrapolation of coronary angiographic data from HeFH males and HeFH females predicted that, on average, coronary stenosis starts at 17 and 25 years of age, respectively ( Figure 2 ).3 Corresponding non-invasive data have been obtained recently by assessing accumulation of coronary plaque burden with computed tomography angiography in a HeFH patient population on suboptimal statin therapy, which had been initiated in adulthood.4 When the plaque burden was extrapolated to age, the data suggested that atherosclerotic plaques may start to develop in HeFH males and females at a mean age of ∼20 and 30 years, respectively. Moreover, the total plaque burden significantly predicted future coronary …