Routine measurements B- and C-cycle: additional information

Routine measurements B- and C-cycle: additional information

LASA file name(s): LASAB860 / LASAC860 / LAS2B860 / LASAG860 / LAS3B860

Contact: Natasja van Schoor


Albumin, total cholesterol and iron are ‘routine measurements’ in LASA. Serum albumin is synthesized by the liver, maintains osmotic pressure, and transports various substances through the bloodstream.1. Total cholesterol is synthesized in many types of tissue, but particularly in the liver and intestinal wall. Approximately three-quarters of cholesterol is newly synthesized and a quarter originates from dietary intake. From several studies evidence is available that low serum albumin predicts all-cause mortality 2-5 and coronary heart disease (CHD) mortality and CHD incidence 4, 6-7, stroke incidence and stroke mortality.8 Low serum total cholesterol predicts higher mortality rates 9-13 and CHD and cancer mortality. 4,11-12 But also high serum total cholesterol levels predicts higher CHD mortality and morbidity.

NOTE: A complete overview of routine measurements, including measurements after the C-cycle, can be found at Blood collection and overview (routine) measurements.

Measurements in LASA

Both serum albumin and total cholesterol levels were determined directly. This blood was analyzed in two laboratories in the B-cycle: in Zwolle in the ISALA clinic (a fusion of ‘de Weezelanden’ and Sofia hospital) and in Amsterdam in the PCA Valeriuskliniek.
Blood collected in the C-cycle in the region Amsterdam was analyzed in the laboratory of the VU University Medical Center in Amsterdam, in the region Zwolle in the ISALA clinic, in the region Oss in the Bernhoven Hospital.


Serum albumin concentration was determined by photometry using a bromocresol-purper method. This method is more sensitive for immunoglobulines than methods used in other labs (esp. at lower values). Total cholesterol was measured using enzymatic colorimetry method with a Roche/Hitachi analyzer.


Serum albumin concentration was determined by BCG (bromocresol green) method.
Total cholesterol was measured using enzymatic CHOD-PAP method. Both blood markers are measured with a Hitachi analyzer (in 1992/93: hitachi 717, in 1995/96: hitachi 917).

See further in this document “Syntax conversion albumin”. All albumin values converted to green method (gold standard) in variable calb_con.

Serum creatinine (umol/L) was measured using the Jaffe alkaline picrate reaction with a Hitachi 747 analyzer. (Note: This method is similar to the kinetic Jaffe method).

Use of laboratories

Take into account that different labs have been used within LASA in the region Amsterdam. This is especially of importance when looking at change in serum levels between B and C (not recommended because of different methods and laboratories!). Another important point is that the VU University Medical Center has lower serum levels in general as compared to the other labs, this is the case for both serum albumin and serum total cholesterol. Bianca Schalk has used the bench marking method to control for between-laboratory differences in albumin. This was not changed in the official files (for further information contact: Jan Poppelaars, data manager LASA).
Information from the Dutch Foundation for Quality Assessment in Clinical Laboratories (SKZL) was used to control for between-laboratory differences. Every 2 months, eight standard serum samples were sent to the laboratories to be analyzed, and the serum albumin concentration was reported to the SKZL. Using linear regression, a regression line was fitted using the individual laboratory assessment of serum albumin for each sample and the overall national mean of the same sample. Separate lines were fitted for each laboratory to adjust the serum albumin levels in the LASA sample.
Serum albumin concentrations (g/L) were determined using a bromcresol green photometric assay with a Hitachi analyzer in the laboratory in Zwolle. The laboratory of the VU University Medical Center used a bromcresol purple method. To make the serum albumin levels comparable, the serum albumin levels that were determined using the bromcresol purple method were converted using a validated formula.14

Availability of data per wave

Table 1. Numbers per wave and the median [range, min-max] of serum albumin, total cholesterol, LDL-, HDL-cholesterol and iron in the B-cycle and C-cycle.

Amsterdam Oss Zwolle No blood samples No valid data Median [range]
Blood B-cycle (n=2671) N=739 N=6611 N=773 N=661(1) +498(2) =1159 N
Albumin 734 0 773 1159 5 45 [31-55]
Total cholesterol 734 0 773 1159 5 6.4 [3.0-11.8]
LDL- cholesterol 0 0 698 1159 5+739 3.92 [0.94-9.25]
HDL- cholesterol 0 0 770 1159 3+739 1.22 [0.58-3.25]
Iron 0 0 773 1159 739 14.8 [2.4-39.0]
Blood C-cycle (n=1509) N=923 N=405 N=181 N
Albumin 922 404 1+1 42 [29.0-54.9]
Total cholesterol 905 404 18+1 5.8 [0.4-40.9]
LDL- cholesterol 0 404 923 +1 3.87 [0.70-9.34]
HDL- cholesterol 0 404 923 + 1 1.33 [0.56-3.56]
Iron 0 404 923 +1 17.0 [5.2-37.7]

(1) No blood was collected in Oss
(2) In part of Amsterdam blood was collected but not determined immediately (498) in the B-cycle

Table 2. The standard in the Netherlands as presented in diagnostic compass (Diagnostisch kompas 1999/2000) written for Physicians and Clinical-chemics.

Markers low Normal / reference High Very high Unit
Albumin * 35 – 55 G/L
Total cholesterol < 5.0 5.0 – 6.4 6.5 – 7.9 > 8.0 Mmol/L
LDL- cholesterol < 3.5 3.5 – 4.4 4.5 – 5.6 5.7 Mmol/L
HDL- cholesterol Men < 0.9

Women < 1.1

Triglycerides** < 2.0 2.0 – 5.9 6.0 – 11.0 Mmol/L
Iron Men 14 – 28

Women 10 – 25


* Patients who lie at least 30 minutes have 6 g/l albumin lower than normal/ reference (35-55 g/L). Patients older than 70 years, have 20 % lower than normal/ reference (35-55 g/L).
** only non-fasting!


Previous use
Hypoalbuminea is commonly defined as <35 g/L, whereas other studies use <=38 g/L.11. For low serum albumin, usually the lowest quintile, quartile or tertile is used. There is no standard definition of hypocholesterolemia, but in several studies a serum level of <=4.2 mmol/L (<= 160 mg/dl) has been used.15 Other commonly used cutpoints are 5.20 mmol/L (200 mg/dL) or 6.20 (240 mg/dL).
Hypercholesterolemia is defined as >8.0 mmol/L (NHG-standaard Cholesterol).

Previous use in LASA

  • Dik, M.G., Jonker, C., Hack, C.E., Smit, J.H., Comijs, H.C., Eikelenboom, P. (2005). Serum inflammatory proteins and cognitive decline in older persons. Neurology, 64, 1371-1377.
  • Kuchuk, N.O., Van Schoor, N.M., Pluijm, S.M.F., Smit, J.H., De Ronde, W., Lips, P.T.A. (2007). The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women. Clinical Endocrinology, 67, 295-303.
  • Schaap, L.A., Pluijm, S.M.F., Smit, J.H., Van Schoor , N.M., Visser, M., Gooren, L.J.G., Lips, P.T.A. (2005). The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clinical Endocrinology, 63, 152-160.
  • Schalk, B.W.M., Deeg, D.J.H., Penninx, B.W.J.H., Bouter, L.M., Visser, M. (2005). Serum albumin and muscle strength: a longitudinal study in older men and women. Journal of the American Geriatrics Society, 53, 1331-1338.
  • Schalk, B.W.M., Visser, M., Bremmer, M.A., Penninx, B.W.J.H., Bouter, L.M., Deeg, D.J.H. (2006). Change of serum albumin and risk of cardiovascular disease and all-cause mortality. American Journal of Epidemiology, 164, 969-977
  • Schalk, B.W.M., Visser, M., Deeg, D.J.H., Bouter, L.M. (2004). Lower levels of serum albumin and total cholesterol and future decline in functional performance in older persons: the Longitudinal Aging Study Amsterdam. Age and Ageing, 33, 3, 266-272.
  • Schalk, B.W.M., Visser, M., Penninx, B.W.J.H., Baadenhuijsen, H., Bouter, L.M., Deeg, D.J.H. (2005). Change in serum albumin and subsequent decline in functional status in older persons. Aging Clinical and Experimental Research, 17, 4, 297-305.

Syntax conversion albumine (PDF, in Dutch)

Total cholesterol, High-Density Lipoprotein (HDL), and Low-Density Lipoprotein (LDL) cholesterol, triglycerides, and fructosamin were also determined in EDTA plasma samples (collected in 1995/96 and since then stored at –80° C at the Department of Clinical Chemistry of the VUmc) in 2005 (LASAC867). An important advantage of the cholesterol values in LASAC867 is that they were done in one laboratory.


  1. Rothschild MA, Oratz M, Schreiber SS. Serum albumin. Hepatology 1988;8(2):385-401.
  2. Corti MC, Guralnik JM, Salive ME, Sorkin JD. Serum albumin level and physical disability as predictors of mortality in older persons [see comments]. JAMA 1994;272(13):1036-42.
  3. Sahyoun NR, Jacques PF, Dallal G, Russell RM. Use of albumin as a predictor of mortality in community dwelling and institutionalized elderly populations [see comments]. J.Clin.Epidemiol. 1996;49(9):981-8.
  4. Weijenberg MP, Feskens EJ, Souverijn JH, Kromhout D. Serum albumin, coronary heart disease risk, and mortality in an elderly cohort. Epidemiology. 1997;8(1):87-92.
  5. Fried LP, Kronmal RA, Newman AB, Bild DE, Mittelmark MB, Polak JF, Robbins JA, Gardin JM. Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. JAMA 1998;279(8):585-92.
  6. Corti MC, Salive ME, Guralnik JM. Serum albumin and physical function as predictors of coronary heart disease mortality and incidence in older persons. J.Clin.Epidemiol. 1996;49(5):519-26.
  7. Nelson JJ, Liao D, Sharrett AR, Folsom AR, Chambless LE, Shahar E, Szklo M, Eckfeldt J, Heiss G. Serum albumin level as a predictor of incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. Am.J.Epidemiol.2000.Mar.1.;151.(5.):468.-77. 151(5):468-77.
  8. Gillum RF, Ingram DD, Makuc DM. Relation between serum albumin concentration and stroke incidence and death: the NHANES I Epidemiologic Follow-up Study. Am.J.Epidemiol. 1994;140(10):876-88.
  9. Harris T, Feldman JJ, Kleinman JC, Ettinger WHJ, Makuc DM, Schatzkin AG. The low cholesterol-mortality association in a national cohort [see comments]. J.Clin.Epidemiol. 1992;45(6):595-601.
  10. Ives DG, Bonino P, Traven ND, Kuller LH. Morbidity and mortality in rural community-dwelling elderly with low total serum cholesterol. J.Gerontol. 1993;48(3):M103-M107.
  11. D’Agostino RB, Belanger AJ, Kannel WB, Higgins M. Role of smoking in the U-shaped relation of cholesterol to mortality in men. The Framingham Study. Am.J.Epidemiol. 1995;141(9):822-7.
  12. Corti MC, Guralnik JM, Salive ME, Harris T, Ferrucci L, Glynn RJ, Havlik RJ. Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons [see comments]. Ann.Intern.Med. 1997;126(10):753-60.
  13. Volpato S, Zuliani G, Guralnik JM, Palmieri E, Fellin R. The inverse association between age and cholesterol level among older patients: the role of poor health status. Gerontology 2001;47(1):36-45.
  14. Schalk, B.W.M., Deeg, D.J.H., Penninx, B.W.J.H., Bouter, L.M., Visser, M. Serum albumin and muscle strength: a longitudinal study in older men and women. Journal of the American Geriatrics Society 2005; 53, 1331-1338.
  15. Reuben DB, Moore AA, Damesyn M, Keeler E, Harrison GG, Greendale GA. Correlates of hypoalbuminemia in community-dwelling older persons. Am.J.Clin.Nutr. 1997;66(1):38-45.


  1. Diagnostisch kompas: voorlichting over aanvullende diagnostiek/ uitgave van het College voor zorgverzekeringen 1999- Amstelveen. Verschijnt twee-jaarlijks, Kompas 1999 eindredacteur dr. H.A.I.M. van Leusden met index ISBN 90-70918-21-8, 2e editie.
  2. NHG-standaard Cholesterol (herziene versie).

Date of last update: March 31, 2020