By: Robert W. Griffith, MD
More findings are emerging to support the concept that inflammation is an integral part of atherosclerosis and coronary heart disease. The latest is a link between heart attacks and raised white blood cell counts . . .
The last few years have brought more and more convincing evidence that inflammation is involved in atherosclerosis1 and the diseases associated with it - heart attack, angina, stroke, and so on. The usual markers for inflammation that have been measured are C-reactive protein (CRP), interleukin-6, and tumor necrosis factor-alpha. A new study has now examined the role of the white blood cell (WBC) count in predicting heart attacks in women. The findings are reported in the Archives of Internal Medicine, and we summarize them here.
The Women's Health Initiative (WHI) Observational Study was used to obtain comprehensive medical information from over 72,000 postmenopausal women throughout the USA who were free of cardiovascular disease and cancer at the baseline examination.
Follow-up was conducted by annual mailed questionnaires, except in year three, when the participants were to attend for a clinical exam. Reports of treatment or hospitalization for any cardiovascular problems obtained at each contact, and led to full assessment by a local physician; death certificates were obtained, where necessary.
The participants were classified into 4 groups, or 'quartiles', according to their baseline total WBC count: 2.5-4.7, 4.7-5.6, 5.6-6.7, and 6.7-15.0 x109/L. The frequency of occurrence of fatal and non-fatal coronary heart disease (i.e. heart attacks), stroke, and deaths from any cause were calculated for each quartile. This allowed comparison between quartiles, and the calculation of the likelihood, or hazard ratio, for each quartile compared with the lowest one (2.5-4.7 x109/L).
At baseline, the average age of the women was 63; 84% were white, 4% had diabetes, 35% had high blood pressure, and 6% smoked. Body mass index (BMI), waist size, and blood pressure - cardiovascular risk factors - were increased with higher WBC levels. On the other hand, alcohol, fiber, fruit, and vegetable intake and physical activity were lower in the higher WBC quartiles.
During the follow-up period, which averaged 6.1 years, there were 187 deaths from heart attack, 701 non-fatal heart attacks, 738 strokes, and 1919 deaths from any cause.
Women in the highest quartile (WBC counts over 6.7 x109/L) were more than twice as likely to have a fatal heart attack (hazard ratio 2.36) than those in the lowest quartile (WBC counts less than 4.7 x109/L). This was after adjusting for individual differences in age, race, diabetes, high blood pressure, smoking, high cholesterol, BMI, alcohol use, diet, physical activity, aspirin use, and hormone use. They also had a 40% greater risk of a non-fatal heart attack, 46% greater risk of stroke, and 50% risk of for death from any cause, compared with the women in the lowest WBC quartile.
Analyses showed that the linkage between WBC level and cardiac events was not associated with the CRP levels measured at baseline. However, in women in the top quartiles for both WBC count and CRP, the likelihood of coronary heart disease was increased nearly 7 times over those women in the lowest quartiles for the two tests.
The study shows that WBC counts over 6.7 x109/L are linked with an increased risk of heart attacks, strokes, and death in older women. People may ask "What about men?" Similar findings were reported for men last year.
It's not known whether the white blood cells are directly involved in the pathological process in the arteries, or are merely another marker of inflammation somewhere in the body. Nevertheless, the relationship seems clear, and, after all, a WBC count is one of the simplest and cheapest lab exams that can be done.
All this shouldn't be taken to mean that a slightly raised WBC count means you are likely to have a heart attack, any more than a slightly raised temperature means you've got pneumonia. Like many lab tests, it provides just another piece of data that the doctor uses in reaching a diagnosis or risk assessment. The importance of the study lies in its indication that inflammatory changes (producing more WBC) are closely linked to cardiovascular events, that's all.
Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women. KL. Margolis, JE. Manson, P. Greenland, et al., Arch Intern Med, 2005, vol. 165, pp. 500--508
1. Atherosclerosis is the process in which deposits of fatty substances, cholesterol, cellular waste products, calcium and other substances build up in the inner lining of an artery, forming a plaque, and hardening the artery.