Relationship to Classical Indexes

It is important to analyze whether the previous analysis methodology for parameterizing the vessel behavior during the flow-mediated dilation test is linked to other clinical parameters and CVD risk factors traditionally used in the medical literature. Serum lipids, particularly cholesterol and the cholesterol fraction carried by low-density lipoproteins (LDL cholesterol) are recognized as a main causal factor of atherosclerosis [34]. In this disease lipids accumulate in the vessel wall, disturbing the vascular function of delivering sufficient blood flow to the affected territories, which ends with the manifestation of a vascular clinical event like heart attack or stroke. Moreover, knowing patients' lipid levels and modifying them with drugs and diet is the main preventive tool against cardiovascular diseases. From this point of view, cholesterol and LDL cholesterol are considered as risk factors, as higher levels identify individuals with higher risk whereas the cholesterol fraction carried by high-density lipopro-teins (HDL cholesterol) is considered as a protective factor. Triglycerides also associate with future cardiovascular disease, and higher levels are present in the metabolic syndrome, which identifies high-risk individuals [34].

Endothelial dysfunction is believed to be a main mechanism through which individuals with unfavorable lipid profiles develop atherosclerosis [35]. As stated before, in the FMD test, the vasodilatory response is identified with endothelial function [1].

5.5.2.1 Sample Population: Clinical and Traditional Variables

A subset of n = 161 subjects from the military male population described in section 5.2.1 was analyzed. This population had normal to mildly unfavorable lipid levels. Also, the subset of subjects used in the following analysis corresponds with the one used in computing the EigenFMD and EigenD analyses of the previous section, and whose FMD curves where obtained with our computerized technique.

Fasting serum samples were obtained from the subjects and were analyzed at the Lozano Blesa University Clinical Hospital (Zaragoza, Spain). Analyses were performed for total cholesterol, triglycerides, and HDL cholesterol by standard enzymatic laboratory techniques. LDL cholesterol was calculated using the Friedewald formula [36,37] in subjects whose triglycerides levels were less than 400 mg/dl.

In each absolute diameter curve, a reference baseline diameter was established before vasodilation, 0basai, in a region free from motion artifacts selected just after cuff pressure release (Fig. 5.11(a)). This diameter was similar in most cases to that measured before cuff inflation, 0r (Fig. 5.11(a)). Peak vasodilation was identified in the curve to calculate AFMDc (Eq. 5.13).

5.5.2.2 Correlation Analysis

Pearson's linear correlation coefficients were computed between eigenmodes coefficients, from both EigenFMD and EigenD, and serum lipids. Correlations were also computed between ROBPCA-derived indexes and traditional vasodilation curve measurements: flow-mediated dilation (AFMDc) and baseline diameter (0basal). Pearson's coefficients between traditional curve measurements and serum lipids were used to control the association that could be expected. In all analyses, statistical significance was assumed when p < 0.05.

Pearson's linear correlation coefficients between traditional curve measurements and serum lipids are shown in Table 5.7.

Pearson's linear correlation coefficients between EigenFMD and EigenD modes coefficients and serum lipids are shown in Tables 5.8 and 5.9, respectively.

Table 5.7: Pearson's correlation coefficient, r (and p values), between serum lipid levels, and classical AFMDc and baseline diameter

Classical index

Cholesterol

Triglycerides

HDL-C

LDL-C

AFMDc

-0.154 (0.051)

0.035 (0.655)

0.190 (0.016)*

-0.255 (0.001)*

0basal

0.015 (0.853)

0.204 (0.009)*

-0.145 (0.067)

-0.012 (0.884)

Table 5.8: Pearson's correlation coefficient, r (and p values), between serum lipid levels and the first five EigenFMD mode coefficients

Mode #

Cholesterol

Triglycerides

HDL-C

LDL-C

EigenFMD 1

G.G5S (G.5G4)

-G.G47 (G.555)

—G.16G (G.G4S)*

G.1S2 (G.G97)

EigenFMD 2

G.1G6 (G.18G)

G.G44 (G.582)

—G.125 (G.115)

G.214 (G.GG7)*

EigenFMD S

G.159 (G.G44)*

-G.GS4 (G.672)

—G.G27 (G.7S4)

G.19S (G.G15)*

EigenFMD 4

G.G16 (G.841)

—G.127 (G.1G8)

—G.G25 (G.75G)

G.G67 (G.4GG)

EigenFMD 5

G.G44 (G.584)

G.18G (G.G22)*

G.G2G (G.8G2)

—G.G11 (G.892)

Statistically significant correlations are indicated with an asterisk. HDL-C: High-density lipoprotein chole-strol; LDL-C: low-density lipoprotein cholestrol.

Statistically significant correlations are indicated with an asterisk. HDL-C: High-density lipoprotein chole-strol; LDL-C: low-density lipoprotein cholestrol.

Finally, Pearson's linear correlation coefficients between EigenFMD and EigenD mode coefficients, and classical AFMDc and basal diameter are reported in Tables 5.10 and 5.11.

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