Statin treatment slows progression of carotid atherosclerosis in children with heterozygous FH
Effect of Rosuvastatin on Carotid Intima-Media Thickness in Children with Heterozygous Familial Hypercholesterolemia: The CHARON Study
Literature - Braamskamp MJAM, Langslet G, McCrindle BW, et al. - Circulation 2017; published online ahead of printBackground
Children with heterozygous familial hypercholesterolemia (HeFH) have endothelial dysfunction and increased carotid intima-media thickness (IMT) [1-3]. Current pediatric guidelines recommend initiation of statin therapy from 8 years onwards with the aim to achieve an LDL-C <3.5 mmol/L (130 mg/dL), in order to prevent accelerated premature atherosclerosis [4,5]. The efficacy and safety of rosuvastatin has been tested recently in HeFH children and adolescents between the ages of 6 and 17 years [6,7].
In this analysis, the effect of robust LDL-C reduction with rosuvastatin for 2 years on carotid IMT was assessed in HeFH children, compared with unaffected and untreated siblings.
Main results
- At baseline, mean (±SD) carotid IMT was significantly greater for the 197 HeFH children compared with the 65 unaffected siblings (0.397±0.049 mm and 0.377±0.045 mm, respectively; P=0.001).
- During 2 years of follow-up, the rate of progression in mean carotid IMT in the treated HeFH children compared with unaffected siblings was 0.0054 mm/y (95% CI: 0.0030 - 0.0082 mm/y) and 0.0143 mm/y (95% CI: 0.0095 - 0.0192 mm/y) (P=0.002), respectively.
- After 2 years, carotid IMT differences between HeFH children and siblings were no longer significant for mean carotid IMT (0.408±0.043 mm and 0.402±0.042 mm, respectively; P=0.2), and for the segments of the internal carotid artery and the carotid bulb (0.360±0.049 mm and 0.355±0.045 mm; P=0.2; 0.429±0.059 mm and 0.430±0.056 mm; P>0.9, respectively). The common carotid artery segment differed between HeFH children and siblings (0.437±0.055 mm and 0.421±0.054 mm, respectively; P=0.03).
- At baseline, the mean of the maximum carotid IMT was greater for children with HeFH compared with the unaffected siblings (0.477±0.070 mm and 0.445±0.056 mm, respectively; P<0.001). In addition, the IMT of all individual carotid segments were greater in HeFH patients.
- During 2 years of follow-up, the maximum carotid IMT in treated HeFH patients tended to regress compared with baseline, while a progression compared with baseline was seen in the unaffected siblings (–0.0014 mm/y; 95% CI: –0.0046 to 0.0022; and 0.0103 mm/y; 95% CI: 0.0039 to 0.0168; respectively; P=0.002).
- After 2 years, differences in maximum carotid IMT were narrowed between HeFH patients and siblings, although children with HeFH still had an increased mean of maximum carotid IMT (0.437±0.055 mm and 0.421±0.054 mm; P=0.04).
- This was also found for the common carotid artery segment (0.487±0.064 mm and 0.468±0.062 mm, respectively; P=0.02), while the difference in IMT of the internal carotid and carotid bulb segments were no longer significant (0.422±0.062 mm and 0.414±0.053 mm, P=0.3; and 0.515±0.056 mm and 0.501±0.067 mm, P=0.1, respectively).
Conclusion
Children with HeFH treated with rosuvastatin had a slower progression of carotid atherosclerosis measured by carotid IMT, diminishing the difference in IMT between them and unaffected siblings.
The rate of progression in carotid IMT was actually less in the HeFH subjects compared with unaffected siblings. This may indicate that more effective therapy also contributes to removal of previously accumulated lipid in the arterial wall; however, further studies are needed to confirm this.
These findings support the value of early initiation of aggressive LDL-C reduction in these patients, for the reduction of their CV risk.
References
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4. Wiegman A, Gidding SS, Watts GF, et al, European Atherosclerosis Society Consensus P. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36:2425-2437.
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6. Avis HJ, Hutten BA, Gagne C, et al. Efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia. J Am Coll Cardiol. 2010;55:1121-1126.
7. Braamskamp MJ, Langslet G, McCrindle BW, et al. Efficacy and safety of rosuvastatin therapy in children and adolescents with familial hypercholesterolemia: Results from the CHARON study. J Clin Lipidol. 2015;9:741-750.
8. Kusters DM, Hutten BA, McCrindle BW, et al. Design and baseline data of a pediatric study with rosuvastatin in familial hypercholesterolemia. J Clin Lipidol. 2013;7:408-413.
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