Albumin and cholesterol

Routine measurements: Albumin and cholesterol


Contact: Natasja van Schoor

Background albumin and total cholesterol
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 (12). 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)(13)(15)(6) and coronary heart disease (CHD) mortality and CHD incidence (3)(10,15) FQUOTE "" stroke incidence and stroke death (7).
Low serum total cholesterol predicts higher mortality rates (8)(9)(4)(1)(14) and CHD and cancer mortality {Corti 1997; Weijenberg 1996; Schatzkin 1988; d’Agostino 1995}. But also high serum total cholesterol levels predicts higher CHD mortality and morbidity.

Measurements
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.

VUmc
Serum albumin concentration was determined by fotometry 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.

Weezelanden
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. (NB: 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 have 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 (ask Jan Poppelaars, LASA datamanager, for method and resulting files M:\projecten\Lasabloed\Biobanking\Benchmarking SKZL - B.Schalk):
"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
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." (Schalk BW et al, JAGS 2005).

Table 1. Total numbers 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

³ 5.7

Mmol/L

HDL- cholesterol

- - -

Men < 0.9

Women < 1.1

Mmol/L

Triglycerides**

-

< 2.0

2.0 - 5.9

6.0 - 11.0

Mmol/L

Iron

-

Men 14 – 28

Women 10 – 25

- -

mmol/L

* 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 is usually used the lowest quintile, quartile or tertile. 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(5). 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). Amerikaanse studies, afkappunten erbij vermelden: framingham studie en USA studies.

Previous use in LASA
Women with low total cholesterol (<= 5.2 mmol/L) were more likely to decline in functional performance compared to serum total cholesterol concentration (>5.2 mmol/L).
Men with combined low serum albumin (<= 43g/L) and low serum total cholesterol(<= 5.2 mmol/L) show also an increased risk for functional decline (Schalk 2002). Also M.Dik and S. Pluijm (16) used serum albumin as a potential confounder (Dik et al., 2003)

Syntax conversion albumine (PDF, in Dutch)

Note

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.

References

  1. 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.
  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. 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.
  4. 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.
  5. Ettinger WHJ, Harris T. Causes of hypocholesterolemia. Coron.Artery.Dis. 1993;4(10):854-9.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. Rothschild MA, Oratz M, Schreiber SS. Serum albumin. Hepatology 1988;8(2):385-401.
  13. 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
  14. 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.
  15. 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.
  16. Dik, M.G., Pluijm, S.M.F., Jonker, C., Deeg, D.J.H., Lomecky, M.Z., Lips, P.T.A. (2003). Insulin-like growth factor I (IGF-I) and cognitive decline in older persons. Neurobiology of Aging, 24, 573-581.

    Other:
  17. 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.
  18. NHG-standaard Cholesterol (herziene versie)