Increased Aortic Valve Calcification in Familial Hypercholesterolemia: Prevalence, Extent, and Associated Risk Factors.
BACKGROUND
Familial hypercholesterolemia is typically caused by LDL receptor (LDLR) mutations that result in elevated levels of LDL cholesterol (LDL-C). In homozygous FH, the prevalence of aortic valve calcification (AoVC) reaches 100% and is often symptomatic.


OBJECTIVES
The objective of this study was to investigate the prevalence, extent, and risk-modifiers of AoVC in heterozygous FH (he-FH) that are presently unknown.


METHODS
Asymptomatic patients with he-FH and 131 non-familial hypercholesterolemia controls underwent CT computed tomography calcium scoring. AoVC was defined as the presence of calcium at the aortic valve leaflets. The extent of AoVC was expressed in Agatston units, as the AoVC-score. We compared the prevalence and extent of AoVC between cases and controls. In addition, we investigated risk modifiers of AoVC, including the presence of LDLR mutations without residual function (LDLR-negative mutations), maximum untreated LDL-cholesterol (maxLDL), LDL-C, blood pressure, and coronary artery calcification (CAC).


RESULTS
We included 145 asymptomatic patients with he-FH (93 men; mean age 52 ± 8 years) and 131 non-familial hypercholesterolemia controls. The prevalence (%) and AoVC-score (median, IQR) were higher in he-FH patients than in controls: 41%, 51 (9-117); and 21%, 21 (3-49) (p < 0.001 and p = 0.007). Age, untreated maxLDL, CAC, and diastolic blood pressure were independently associated with AoVC. LDLR-negative mutational he-FH was the strongest predictor of the AoVC-score (OR: 4.81; 95% CI: 2.22 to 10.40; p = <0.001).


CONCLUSIONS
Compared to controls, he-FH is associated with a high prevalence and a large extent of subclinical AoVC, especially in patients with LDLR-negative mutations, highlighting the critical role of LDL-C metabolism in AoVC etiology.
['Ten Kate|Gert-Jan R|GR|', 'Bos|Sven|S|', 'Dedic|Admir|A|', 'Neefjes|Lisan A|LA|', 'Kurata|Akira|A|', 'Langendonk|Janneke G|JG|', 'Liem|Anho|A|', 'Moelker|Adriaan|A|', 'Krestin|Gabriel P|GP|', 'de Feyter|Pim J|PJ|', 'Roeters van Lennep|Jeanine E|JE|', 'Nieman|Koen|K|', 'Sijbrands|Eric J|EJ|']
D001021:Aortic Valve D001024:Aortic Valve Stenosis D002114:Calcinosis D002118:Calcium D004247:DNA D004452:Echocardiography D005260:Female D006801:Humans D006938:Hyperlipoproteinemia Type II D008074:Lipoproteins D008297:Male D008875:Middle Aged D009154:Mutation D009426:Netherlands D015995:Prevalence D012189:Retrospective Studies D012307:Risk Factors D014057:Tomography, X-Ray Computed
aortic valve calcification familial hypercholesterolemia LDLR-negative mutation coronary artery calcification calcific aortic stenosis low-density lipoprotein receptor