PLURALIDAD DEL YO

Reliable and precise measurements of lipoproteins are important for the studies undertaken in this Thesis. The lipoprotein levels used for the studies presented in Chapters 4 and 8 were performed in the Woden Valley Hospital Biochemistry Department, which participates in an external quality control programme and obtains good results for reliability and precision. In the main case-control study (described in Chapter 3) the levels were measured in two laboratories, and the comparison was used to confirm the reliability of the results used for the other studies described in Chapters 4 and 8 of this Thesis. In addition, in this section the validity of the rela­ tionship of lipoproteins with angiographically defined CAD is evaluated utilising lipoprotein measurements from the two different laboratories. The results also provide support for the angiographic scoring system used in the studies and de­ scribed in Chapter 8.

5.1.2 Methods

5.1.2.1 Patients. The case group of young male subjects with CHD used in this evaluation is described in Chapter 3.

5.1.2.2 Blood lipid measurements. The methods for the blood lipid measure­ ments are described in Chapter 2.

5.1.3 Results

5.1.3.1 Cholesterol levels. The cholesterol level of those subjects for whom it was available before or at the time of their diagnosis (n=27) was significantly higher than the levels at the time of the study (Table 5.1)

5.1.3.1 Comparison of cholesterol levels. An analysis of variance was per­ formed to compare all the cholesterol levels. The variance between the group means was significantly larger than among the average variance within groups. Thus there are sig n ific a n t d ifferen ces for the values of the group m eans (F = 4.7468, p=0.0033). After correcting for multiple comparisons so that the probability was only 5% that any one or more of the comparisons would be significant with p<0.05 by chance alone, a significant difference was only found between the prior cholest­ erol level and the study level (Table 5.2). Small but non significant differences (when corrected for multiple comparisons) were found between the serum cholester­ ol levels from the study laboratory, the values from the service laboratory and the plasma cholesterol levels from the service laboratory (Table 5.2).

5.1.3.2 Comparison of cholesterol levels. The correlation coefficient between the standard laboratory serum cholesterol and the service laboratory was high, with a correlation coefficient (r) of 0.93, standard error for the equation (SEE) of 2.76, an intercept of 0.10, and slope of 0.77 (SE of the slope=0.04). The same analysis between the standard laboratory serum cholesterol measure and the plasma cholest­ erol from the service lab o rato ry gave a c o rre latio n c o efficien t of r= 0.90,

SEE=3.31, intercept=0.18 and slope=0.59 (SE of the slope=0.04). The service laboratory serum measurements were slightly higher and became greater with in­ creasing values, although the differences were small. The plasma values correspond­ ed accurately throughout the measured range but were consistently and modestly higher than the standard laboratory values.

5.1.3.3 Comparison with angiographic scores. The previous cholesterol meas­ urement (for those patients having had the level documented), was inversely related to the number of normal segments, and directly correlated with the extent of disease (CAS, mCAS and pCAS), as well as the number of mild and moderate lesions (25- 50% and 50-75%) (Table 5.3). The serum cholesterol level from the standard labo­ ratory had similar relationships, as did the plasma and serum cholesterol from a service laboratory (Table 5.3). The apoprotein B levels had identical or possibly more significant relationships to the extent of disease, the number of mild and moderate lesions and the number of normal segments than did the cholesterol levels (Tables 5.3, 5.4 and 5.5).

Triglyceride levels from both laboratories had no consistent relationships with the extent and severity of disease, although there was a positive association with the number of normal segments (Tables 5.3, 5.4 and 5.5). The HDL cholesterol had no consistent relationship with any of the angiographic measurements (Tables 5.3, 5.4 and 5.5). Equally, apoprotein A1 levels were not related to any of the angiographic measures (Tables 5.3, 5.4 and 5.5). These associations will be further evaluated and discussed in the following section of this Chapter.

5.1.4 Discussion

In this section, the relationship between total serum cholesterol from a research laboratory (used as the standard laboratory) with well established quality control methods, as well as the level in serum and plasma taken from the same blood sample and measured in a service laboratory, also with a well established quality control programme, have been compared. The linear correlation was similar with all meas­ ures.

The service laboratory maintains an external and internal quality control programme and has a CV close to 3% with an external standard, a level aimed for with such external standardisation.361,585,586 Sustaining both precision and accuracy of meas­ urements by utilisation of external quality controls is the "sine quo non" for the measurement of cholesterol for clinical use.585,586 The results demonstrate that measurement of cholesterol by a service laboratory, which maintains good quality control methods, can provide results of sufficient accuracy to compare to the results from the rigorous standards of a standard laboratory, and this included a measurable relationship with CAD. Plasma levels had a slightly higher level which was not sta­ tistically significant. Small differences resulting in reduced accuracy of estimating the true mean have previously been noted using various anticoagulants.361 However, the reliability would appear to be maintained as the predicted univariate association with CAD is sustained.

prior to the study in those patients for whom it was available, and the measurements taken at the time of the study, often many months after the diagnosis. Numerous confounding factors may contribute to such a difference, such as changes in diet and other sources of clinical variation,586 in addition to the effect of regression to the mean of repeated measurements.370 In view of the probability of dietary changes having an effect on the current cholesterol level, the previous measurement would be expected to more accurately reflect premorbid levels, and hence have a relationship with CAD as demonstrated. Indeed, the previous cholesterol, in those patients for whom it was available, appears to have a stronger relationship with the extent of coronary atherosclerosis than the levels measured at the time of the angiographic assessment.

5.1.5 Summary

1. These results demonstrate that cholesterol measurements from a service laboratory with appropriate quality control methods can provide information that is both precise, accurate and relevant to the disease process. The reliability for the clinical use of results from a service laboratory with thorough quality control is well validated.

2. The measurements of cholesterol performed in the Woden Valley Hospital Biochemistry Department are of sufficient reliability and precision to be used as a measure in studies assessing potential confounding factors as described in Chapters 4 and 8.

5.2 THE RELATIONSHIP BETWEEN BLOOD LIPOPROTEINS