FMD Response Eigen Parameterization

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As can be concluded from Table 5.7, a weak but significant correlation was found between AFMDc and LDL cholesterol in a damaging way and between AFMDc and HDL cholesterol in a protective way. This had been previously reported when studying dyslipidemic populations with a similar correlation magnitude, association that could be slightly attenuated in our population due to a narrower range of lipids variation. For instance, Kuvin et al. [38] found a correlation coefficient of HDL cholesterol and AFMDc of 0.3. The correlation between classical flow-mediated dilation and LDL cholesterol (r = -0.40) had been previously reported by Aggoun et al. [39] in hypercholesterolemic patients. Other studies report one of these associations but rarely both or with stronger association coefficients [40] and never in natural large populations with normal lipid levels [41].

Triglycerides correlated significantly with baseline diameter, 0basal. The presence of wider vessels has been described for high-risk [38] and atherosclerotic [41] individuals.

The sign associated to the coefficients of EigenFMD and EigenD modes is contingent. These coefficients represent the projections of sample vectors along the eigenvectors of a robust covariance matrix. Since the eigenvectors could equally have been selected with reverse directions the sign of the correlation ratio has to be interpreted in consonance with the eigenmode plots of Figs. 5.12 and 5.13. On the contrary, the effect of risk factors on the direction of variation of the EigenFMD and EigenD curves is not arbitrary and, therefore, they will be discussed in the sequel.

Among the EigenD modes in Fig. 5.13, the first mode, which broadly represents baseline diameter, significantly correlates with triglycerides, while EigenD mode number 2 does with LDL cholesterol. This later mode graphically appears to represent dilation and diameter decay (the lower the LDL cholesterol level, the higher the peaks and the quicker the vessel recovery).

EigenFMD modes are also related to cholesterol fractions. Interestingly, this analysis highlights that each fraction exerts a different influence on the curve shape. While HDL cholesterol covaries with the first mode, which could be interpreted as a classical measure of FMD peak (the higher the HDL cholesterol level, the higher the peaks), LDL cholesterol is significantly associated with the second mode, which has a form similar to EigenD 2 (the higher the LDL cholesterol levels, the lower the peaks and the slower the decays), and EigenD 3, interpretable as response velocity or time-to-peak (the higher LDL-cholesterol values, the later the peaks).

The classical measurement of FMD, AFMDc, correlates with statistical significance with almost all absolute and relative shown eigenmodes. The mode with the highest correlation is EigenFMD 1 (r = -0.786), which one can visually argue that captures the maximum dilation peak. Other modes with correlation coefficients over 0.300 are also present but their visual interpretation is more subtle.

EigenD 1 is almost equivalent to the baseline diameter. This is promising, as this manual measurement could be potentially estimated on an observer-independent basis. Baseline diameter also showed significant correlations with EigenFMD 2 and 4 although the interpretation of this fact is not so evident.

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