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Etiology

Fibrinogen, viscosity, and leukocyte count predicted ischemic heart disease in middle-aged men

ACP J Club. 1991 July-Aug;115:29. doi:10.7326/ACPJC-1991-115-1-029


Source Citation

Yarnell JW, Baker IA, Sweetnam PM, et al. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation. 1991 Mar;83:836-44.


Abstract

Objective

To determine whether fibrinogen, viscosity, and leukocyte count predict ischemic heart disease in middle-aged men.

Design

2 age- and sex-defined cohorts were followed for 3 and 5 years (Caerphilly and Speedwell Collaborative Heart Disease Studies).

Setting

Community-based study in Wales, United Kingdom.

Participants

All middle-aged men living near Caerphilly and those enrolled in 16 general practices in Speedwell were approached (n = 5368). 4860 men were recruited; analysis was based on 4641 men (86% of those approached).

Assessment of risk factors

Medical and smoking history, height, weight, blood pressure, and a 12-lead electrocardiogram (ECG) were recorded. A chest pain questionnaire was administered. Fasting blood samples were measured for fibrinogen (nephelometric method), plasma viscosity (Harkness viscometer), and leukocytes (Coulter S-plus).

Main outcome measures

Death certificates for the sample and notifications of admissions to local hospitals for ischemic heart disease (International Classification of Disease codes 410 through 414) were obtained. Follow-up chest pain questionnaires were obtained for 4399 men, and 4296 had a repeat ECG. Decisions on whether deaths were caused by ischemic heart disease and on occurrence of events (clinical acute myocardial infarction or ECG-defined myocardial infarction [World Health Organization criteria]), were made {without access to study blood-test data}*; medical records were used where available.

Main results

126 of 238 deaths (53%) occurring during the follow-up period were judged to be from ischemic heart disease; 97 clinical nonfatal myocardial infarctions (39%) and 28 ECG-defined myocardial infarctions (11%) occurred. 233 of the 251 major ischemic events (93%) occurred among those who had provided a blood sample. Relative odds (RO) of ischemic events increased as fibrinogen, viscosity, and leukocyte count increased. For the highest quintiles ROs were 4.1 (95% CI 2.6 to 6.5) for fibrinogen, 4.5 (CI 2.8 to 7.4) for viscosity, and 3.2 (CI 2.0 to 4.9) for leukocyte count. After adjustment for risk factors, including pre-existent ischemic heart disease, ROs of major ischemic events showed a similar pattern with ROs of 2.6 (CI 1.6 to 4.3) for fibrinogen, 3.2 (CI 1.8 to 5.6) for viscosity, and 2.2 (CI 1.3 to 3.5) for leukocyte count.

Conclusion

Fibrinogen, viscosity, and leukocyte count were independent predictors of ischemic heart disease in an unselected group of middle-aged men.

Source of funding: Not stated.

Address for article reprint: Mr. P.M. Sweetnam, MRC Epidemiology Unit, Leandough Hospital, Penarth, South Glamorgan CF6 IXX, Wales, UK.

*Information supplied by aurthor.


Commentary

The results of this carefully analyzed cohort study strongly argue for the importance of total leukocyte count, fibrinogen, or plasma viscosity, or a combination, as predictors of coronary heart disease in middle-aged white men. Fibrinogen was previously shown to be an independent risk factor for coronary heart disease over 12 years for both men and women (1), and the upper tertile of total leukocyte count was found to have an odds ratio of 1.53 for ischemic heart disease after adjustment for other risk factors (2). This is the first study, according to the authors, that has examined plasma viscosity and its relation to coronary heart disease.

All 3 variables are increased with smoking. This study shows, however, that when smoking is taken into account, although the significance of these 3 variables as predictors of coronary heart disease is lessened, the odds ratio remains near 2.0, which approximates the odds ratios of risk factors such as severe obesity, hypercholesterolemia, and hypertension. Unfortunately, glucose intolerance, associated with increased fibrinogen levels, was not measured and its relation to these variables could not be studied.

One might speculate that increased plasma viscosity, fibrinogen, and leukocyte count may somehow add to the local rheologic, thrombogenic effects of stenotic arteries to produce more clinical events in those with higher levels.

As the authors of this provocative epidemiologic study indicate, the implications of the study for public health and for the formulation of therapeutic recommendations need further investigation.

Donald Smith, MD
Mount Sinai School of MedicineNew York, New York, USA


References

1. Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA. 1987;258:1183-6.

2. Grimm RH, Neaton JD, Ludwig W. Prognostic importance of the leukocyte count for coronary, cancer, and all cause mortality. JAMA. 1985;245:1932-7.