DIRECT M E A S U R E M E N T
whole blood samples. A n n Clin Biochem 1991; 28: 155-9. 4. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502. 5. Richmond W: Preparation and properties of a cholesterol oxidase from Nocardia Sp. and its application to
OF LDL IN W H O L E B L O O D
the enzymatic assay of total cholesterol in serum. Clin Chem 1973; 19: 1350-6. 6. Jacobs NJ, VanDemark PJ: The purification and properties of the a-Glycerophosphate oxidizing enzyme of Streptococcus faecalis 10C1. Arch Biochem Biophys 1960; 88: 250-5. 7. Deming WE: Statistical adjustment of data. 1st ed. Chichester: Wiley and Sons, 1943.
Clin Biochern, Vol. 25, pp. 403-405, 1992
0009-9120192 $5.00 + .00 Copyright o 1992 The Canadian Society of Clinical Chemists.
Printed in the USA. All rights reserved.
Plasma Fibrinogen" Its Relationship With Oral Contraception, the Menopause, and Hormone Replacement Therapy AMANDA J. LEE, 1 GORDON D.O. LOWE,2 WILLIAM C.S. SMITH, 3 and HUGH TUNSTALL-PEDOE 1 1Cardiovascular Epidemiology Unit, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK, 2University Department of Medicine, Royal Infirmary, Glasgow, G31 2ER, UK, and 3The Leprosy Mission, Katong, P.O. Box 149, Singapore 9143 Introduction Coronary risk factors associated exclusively with women include oral contraceptive use, the menopause and hormone replacement t h e r a p y (HRT). Plasma fibrinogen, an increasingly recognised risk factor for coronary heart disease (CHD), has been reported to be increased among oral contraceptive users (1-3) and among postmenopausal women (4). However, the effect of HRT on plasma fibrinogen has not been reported to date. Using data from both the Scottish Heart Health S t u d y (SHHS) (5) a n d t h e a s s o c i a t e d Scottish MONICA survey (6), we report the effects of oral contraceptive use, the menopause, and HRT on plasma fibrinogen levels among 5,893 women aged 2 5 - 6 4 years. Methods As part of the SHHS 5,236 women aged 4 0 - 5 9 were screened from 22 local authority districts of Scotland (5). In addition, to meet the requirements of the WHO MONICA survey (6), an extended age range of 2 5 - 6 4 years was used in the Edinburgh and North Glasgow districts. This added 757 women giving a total female population of 5,893 aged 2 5 - 6 4 years. Within an extensive questionnaire, women were asked if they had ever taken the contraceptive pill, if yes, for how m a n y years and also if they were still m e n s t r u a t i n g . The B r i t i s h N a t i o n a l F o r m u l a r y (BNF) was used to code any current medication (7). Women who listed an oestrogen-only based (BNF
Correspondence: Amanda J. Lee. Manuscript received February 28, 1992; revised May 15, 1992; accepted May 19, 1992. CLINICALBIOCHEMISTRY,VOLUME 25, OCTOBER 1992
code 6.4.1.1) or a combined (BNF code 6.4.1.3) preparation were taken to be on HRT. Women on any other medication for HRT were excluded from this part of the analysis. No information was available on the doses of any medication, nor on the time interval since the contraceptive pill was last used. Plasma fibrinogen was measured on 4,837 samples of stored citrated plasma using the method of Clauss (8). STATISTICAL METHODS The Student's t-test was used to examine differences in mean values. The multiple linear regression procedure from SPSS-X was used to test the independent contributions of oral contraceptive pill use, the menopause and HRT on plasma fibrinogen levels. The common risk factors; age (years), smoking status (current, ex and never), body mass index (kg/m2), HDL- and total cholesterol (mmol/L), and diastolic blood pressure (mmHg) were controlled for as they have been shown to influence plasma fibrinogen levels in this population (9). A forward stepping procedure was used. Results No significant difference in plasma fibrinogen was found between those 13 women who were currently taking the contraceptive pill (2.43 g/L, SD = 0.28) and those 2,104 women who had previously t a k e n it (2.29 g/L, SD = 0.65). Hence, these two groups were combined. Women with a history of contraceptive pill use had significantly lower plasma fibrinogen levels t h a n women with no history, even aider direct standardisation for both age and smoking status (2.34 g/L, SD = 0.22, n = 2,116 versus 2.40 g/L, SD = 0.23, n = 2,694 respectively, p < 0.001). There 403
LEE, LOWE, SMITH, AND TUNSTALL-PEDOE
TABLE 1 Results of a Multiple Regression Model With Plasma Fibrinogen as the Dependent Variable
Variable Age Smoking status Current vs never Former vs never Body mass index Total cholesterol HDL-cholesterol Diastolic blood pressure Menopausal state Hormone replacement therapy History of contraceptive pill use
Regression Coefficient
Standard Error
p-Value
0.007
0.002
whole blood samples. A n n Clin Biochem 1991; 28: 155-9. 4. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502. 5. Richmond W: Preparation and properties of a cholesterol oxidase from Nocardia Sp. and its application to
OF LDL IN W H O L E B L O O D
the enzymatic assay of total cholesterol in serum. Clin Chem 1973; 19: 1350-6. 6. Jacobs NJ, VanDemark PJ: The purification and properties of the a-Glycerophosphate oxidizing enzyme of Streptococcus faecalis 10C1. Arch Biochem Biophys 1960; 88: 250-5. 7. Deming WE: Statistical adjustment of data. 1st ed. Chichester: Wiley and Sons, 1943.
Clin Biochern, Vol. 25, pp. 403-405, 1992
0009-9120192 $5.00 + .00 Copyright o 1992 The Canadian Society of Clinical Chemists.
Printed in the USA. All rights reserved.
Plasma Fibrinogen" Its Relationship With Oral Contraception, the Menopause, and Hormone Replacement Therapy AMANDA J. LEE, 1 GORDON D.O. LOWE,2 WILLIAM C.S. SMITH, 3 and HUGH TUNSTALL-PEDOE 1 1Cardiovascular Epidemiology Unit, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK, 2University Department of Medicine, Royal Infirmary, Glasgow, G31 2ER, UK, and 3The Leprosy Mission, Katong, P.O. Box 149, Singapore 9143 Introduction Coronary risk factors associated exclusively with women include oral contraceptive use, the menopause and hormone replacement t h e r a p y (HRT). Plasma fibrinogen, an increasingly recognised risk factor for coronary heart disease (CHD), has been reported to be increased among oral contraceptive users (1-3) and among postmenopausal women (4). However, the effect of HRT on plasma fibrinogen has not been reported to date. Using data from both the Scottish Heart Health S t u d y (SHHS) (5) a n d t h e a s s o c i a t e d Scottish MONICA survey (6), we report the effects of oral contraceptive use, the menopause, and HRT on plasma fibrinogen levels among 5,893 women aged 2 5 - 6 4 years. Methods As part of the SHHS 5,236 women aged 4 0 - 5 9 were screened from 22 local authority districts of Scotland (5). In addition, to meet the requirements of the WHO MONICA survey (6), an extended age range of 2 5 - 6 4 years was used in the Edinburgh and North Glasgow districts. This added 757 women giving a total female population of 5,893 aged 2 5 - 6 4 years. Within an extensive questionnaire, women were asked if they had ever taken the contraceptive pill, if yes, for how m a n y years and also if they were still m e n s t r u a t i n g . The B r i t i s h N a t i o n a l F o r m u l a r y (BNF) was used to code any current medication (7). Women who listed an oestrogen-only based (BNF
Correspondence: Amanda J. Lee. Manuscript received February 28, 1992; revised May 15, 1992; accepted May 19, 1992. CLINICALBIOCHEMISTRY,VOLUME 25, OCTOBER 1992
code 6.4.1.1) or a combined (BNF code 6.4.1.3) preparation were taken to be on HRT. Women on any other medication for HRT were excluded from this part of the analysis. No information was available on the doses of any medication, nor on the time interval since the contraceptive pill was last used. Plasma fibrinogen was measured on 4,837 samples of stored citrated plasma using the method of Clauss (8). STATISTICAL METHODS The Student's t-test was used to examine differences in mean values. The multiple linear regression procedure from SPSS-X was used to test the independent contributions of oral contraceptive pill use, the menopause and HRT on plasma fibrinogen levels. The common risk factors; age (years), smoking status (current, ex and never), body mass index (kg/m2), HDL- and total cholesterol (mmol/L), and diastolic blood pressure (mmHg) were controlled for as they have been shown to influence plasma fibrinogen levels in this population (9). A forward stepping procedure was used. Results No significant difference in plasma fibrinogen was found between those 13 women who were currently taking the contraceptive pill (2.43 g/L, SD = 0.28) and those 2,104 women who had previously t a k e n it (2.29 g/L, SD = 0.65). Hence, these two groups were combined. Women with a history of contraceptive pill use had significantly lower plasma fibrinogen levels t h a n women with no history, even aider direct standardisation for both age and smoking status (2.34 g/L, SD = 0.22, n = 2,116 versus 2.40 g/L, SD = 0.23, n = 2,694 respectively, p < 0.001). There 403
LEE, LOWE, SMITH, AND TUNSTALL-PEDOE
TABLE 1 Results of a Multiple Regression Model With Plasma Fibrinogen as the Dependent Variable
Variable Age Smoking status Current vs never Former vs never Body mass index Total cholesterol HDL-cholesterol Diastolic blood pressure Menopausal state Hormone replacement therapy History of contraceptive pill use
Regression Coefficient
Standard Error
p-Value
0.007
0.002
