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4 49 | Rebuttal AoVC in FH This study complies with the Declaration of Helsinki, the institution’s human research committee approved the study protocol and all patients gave written informed consent. CT calcium score To quantify the AoVC, as well as the coronary calcium score, a cardiac CT scan without contrast medium was performed, which enabled calcium scoring at high accuracy and reproducibility (20,21). All CT scans were performed on a dual source CT scanner (first 232 scans: Somatom Definition, last 44 scans: Somatom Definition FLASH, Siemens Medical Solutions, Forchheim, Germany), with application of a prospectively ECG- triggered scan protocol with a tube current of 76 mAs at 70% of the RR-interval. Images were reconstructed with a slice thickness of 3 mm and an increment of 1.5 mm using a medium convolution kernel (B35f ). Lesions were classified as AoVC if located within the aortic valve leaflets, exclusive of the aortic annulus or coronary arteries, and contained 3 or more contiguous pixels with an attenuation value of more than 130 Houndsfield units (2,21). The AoVC-score was defined as the quantity of AoVC expressed in Agatston units, by the same lesion definition as for coronary artery calcium quantification (CAC), using dedicated software (MMWP, Siemens Medical Solutions, Forchheim, Germany) (22). The CT reading was performed blinded with regard to patient characteristics. The absence of AoVC was assigned a score of 0. Additional information about the scan protocol, including the quantification of coronary artery calcium (CAC) has been previously published (23). Contrast-enhanced scans were consulted if the exact location of calcified lesions, in the valve or aortic root, were unclear. Statistical analysis Categorical variables were expressed as numbers (percent). Normally distributed continuous variables were shown as mean (± SD) and skewed variables as median (IQR). To determine the differences between he-FH patients and NACP patients we used a Pearson Chi-Square test to compare binary variables. Continuous variables with a normal distribution were tested with a T-test, and skewed variables were tested with a Mann-Whitney-U test. Statistical significance was considered at a two-sided P-value of < 0.05. We compared the prevalence of AoVC and the AoVC-scores between he-FH and NACP patients, in relationship to age. Age categories were chosen on the basis of equal patient numbers in all groups (N = 92, N = 92 and N = 92).

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