Cholesterol, triglycerides and fructosamin

Cholesterol, triglycerides and fructosamin

LASA filenames: LASAC867

Contact: Natasja van Schoor

Background
For determination of the metabolic syndrome in LASA, total cholesterol, High-Density Lipoprotein (HDL), triglycerides, and fructosamin were determined in a central laboratory. The concentration of Low-Density Lipoprotein (LDL) cholesterol was calculated.

Note: cholesterol was also assessed as a routine measurement in the local laboratories (see documentation “Routine measurements B- and C-cycle: additional information”).

Measurement in LASA

Blood collection
At cycle C (1995/1996), morning blood samples were drawn (n=1352). Subjects were only allowed to take tea and toast, but no dairy products. Total cholesterol, High-Density Lipoprotein (HDL), triglycerides, and fructosamin could be determined in 1287-1298 subjects (see Availability of data per wave).

Measurement procedure & variable information
Fructosamin was determined by a colorimetric test, and HDL cholesterol and triglycerides by an enzymatic colorimetric test (Roche diagnostics, Mannheim, Germany). The interassay coefficient of variation (CV) was <2.8% for fructosamin and triglycerides, and <6.4% for HDL cholesterol. All laboratory analyses (HDL cholesterol, triglycerides, and fructosamin) were performed in EDTA plasma samples, stored at –80° C, at the Department of Clinical Chemistry of the VUmc in 2005. LDL-cholesterol was calculated as total cholesterol – HDL-cholesterol – VLDL-cholesterol; VLDL-cholesterol was calculated as 0.456 x total triglyceride concentration expressed in mmol/L (Friedewald).1 This was done only for triglyceride levels of < 5.0 mmol/L.

The concentration of LDL-cholesterol is usually calculated by the formula of Friedewald et al.1, because isolation of the LDL fraction requires ultracentrifugation, a technique not generally available in service laboratories. The Friedewald formula provides an adequate estimate of LDL-cholesterol for most fasting specimens but is known to be less reliable as triglyceride concentration increases.2 Therefore, the formula was only used if triglycerides were < 5.0 mmol/L. LDL cholesterol could not be calculated in 9 subjects, because triglyceride levels were >= 5.0 mmol/L in these subjects.

Total cholesterol and its metabolites 24S- and 27-hydroxycholesterol were extracted from serum by chloroform/methanol and determined after derivatization to the corresponding trimethylsilyl-ethers by gas chromatography-flame ionization detection (GC-FID) and gas chromatography–mass spectrometry (GC–MS) as reported previously.3Identity of all sterols was confirmed by comparison with the full-scan mass spectra of the authentic compounds. The intra-assay and inter-assay coefficients of variation for all sterols were less than 4% of the respective mean values (precision). Inter-assay accuracy was lower than 3% of the respective nominal values. The limit of quantification was 1 mg/dl for cholesterol and 5 ng/ml for the oxysterols. The ratio of 24S- and 27-hydroxycholesterol to cholesterol were defined as the absolute amount of 24S- and 27-hydroxycholesterol divided by the absolute amount of cholesterol.4

Details of the assay methods and interassay CVs are given in Table 1.

Table 1. Assay methods used at the Dept of Clinical Chemistry of the Vumc, in 2005.

Availability of data per wave

Number of respondents per measurement in wave C

• Total cholesterol: 1296
• HDL cholesterol: 1295
• LDL cholesterol: 1287
• Triglycerides: 1296
• Fructosamin: 1298

Previous use in LASA
(Components of) the metabolic syndrome have been associated with cognitive decline (Dik et al., 2007) and with depression (Vogelzangs et al., 2009).Cholesterol has been used as marker of cognitive decline and dementia by Comijs et al. (2006). Research of Van den Kommer (2012) shows that lower cholesterol absorption, i.e., lower ratios of campesterol and sitosterol to cholesterol, as well as a higher rate of cholesterol synthesis relative to absorption were associated with lower information processing speed. Van den Kommer et al. (2009) suggest that a lower total cholesterol may be considered as a frailty marker, being predictive of lower cognitive functioning in elderly. Oosterweff et al. (2011) observed an association between vitamin D deficiency and the metabolic syndrome. She concluded that this association was mainly determined by the components low HDL and (high) waist circumference. Research of Van Bunderen et al. (2013) showed that in older people, high-normal IGF1 levels are associated with prevalent metabolic syndrome and high triglycerides. Oosterwerff et al. (2013) concluded that low plasma osteocalcin levels are strongly associated with the metabolic syndrome in an older community-dwelling population.

• Comijs HC, Dik MG, Rijmen F, Jonker C, van den Kommer TN, Deeg DJH. Vroege predictoren van dementie, de constructie van beslisbomen. Tijdschr Gerontol Geriatr 2006; 37:237-243.
• Dik, M.G., Jonker, C., Comijs, H.C., Deeg, D.J.H., Kok, A., Yaffe, K., Penninx, B.W.J.H. . Contribution of metabolic syndrome components to cognition in older individuals. Diabetes Care, 2007; 30, 10, 2655-2660.
• Oosterwerff, M.M., Eekhoff, E.M.W., Heymans, M.W., Lips, P.T.A., Van Schoor , N.M. Serum 25-hydroxyvitamin D levels and the metabolic syndrome in older persons: a population-based study. Clinical Endocrinology, 2011;75, 5, 608-613.
• Oosterwerff, M.M., Van Schoor , N.M., Lips, P.T.A., Eekhoff, E.M.W. Osteocalcin as a predictor of the metabolic syndrome in older persons: a population-based study. Clinical Endocrinology, 2013;78, 242-247.
• Van Bunderen, C.C., Oosterwerff, M.M., Van Schoor , N.M., Deeg, D.J.H., Lips, P.T.A., Drent, M.L. Serum IGF1, metabolic syndrome, and incident cardiovascular disease in older people: a population-based study.European Journal of Endocrinology, 2013;168, 393-401.
• Van den Kommer, T.N., Dik, M.G., Comijs, H.C., Fassbender, K., Jonker, C. Total cholesterol and oxysterols: Early markers for cognitive decline in elderly? Neurobiology of Aging, 2009;30, 534-545.
• Van den Kommer, T.N., Dik, M.G., Comijs, H.C., Lutjohann, D., Lips, P.T.A., Jonker, C., Deeg, D.J.H. The role of extracerebral cholesterol homeostasis and ApoE e4 in cognitive decline. Neurobiology of Aging, 2012;33, 622.e17-622.e28.
• Vogelzangs, N., Beekman, A.T.F., Dik, M.G., Bremmer, M.A., Comijs, H.C., Hoogendijk, W.J.G., Deeg, D.J.H., Penninx, B.W.J.H. Late-life depression, cortisol and the metabolic syndrome (Brief report). American Journal of Geriatric Psychiatry, 2009;17, 8, 716-721.
• Van Ancum, J.M., Jonkman, N.H., Van Schoor , N.M., Tressel, E., Meskers, C.G.M., Pijnappels, M., Maier, A.B.. Predictors of metabolic syndrome in community-dwelling older adults. PLoS One 2018; 13, 10, e0206424, 1-12.

References

1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
2. Rifai N, Warnick GR, McNamara JR, Belcher JD, Grinstead GF, Frantz ID, Jr. Measurement of low-density-lipoprotein cholesterol in serum: a status report. Clin Chem 1992;38:150-160.
3. Lütjohann D, Stroick M, Bertsch T, Kühl S, Lindenthal B, Thelen K, Andersson U, Björkhem I, Bergmann Kv, Fassbender K. High doses of simvastatin, pravastatin, and cholesterol reduce brain cholesterol synthesis in guinea pigs. Steroids. 2004 Jun;69(6):431-8. PubMed PMID: 15219793.
4. Van den Kommer, T.N., Dik, M.G., Comijs, H.C., Fassbender, K., Jonker, C. Total cholesterol and oxysterols: Early markers for cognitive decline in elderly? Neurobiology of Aging 2009; 30, 534-545.

Date of last update: March 31, 2020