The More You Run
Physical activity has an inverse relationship with a variety of factors related to inflammation and hemostasis—a fact that could explain why exercise seems to ward off cardiovascular disease, according to British researchers in a report in this week’s issue of Circulation (Circulation. 2002;105:1785–1790).
Twenty years after they screened 7735 men aged 40 to 59 in 24 British towns, a group of researchers from the Royal Free Hospital School of Medicine in London, the University Department of Medicine at the Royal Infirmary in Glasgow, and the Department of Public Health Sciences at St George’s Medical School in London reexamined 4252 of the available survivors, who were now aged 60 to 80. After some men were excluded for incomplete information or other factors, the researchers analyzed information from a fasting blood sample taken from 3810.
They found that physical activity had a statistically significant and inverse relationship with fibrinogen, plasma and blood viscosity, platelet count, coagulation factors VIII and IX, von Willebrand factors, fibrin D-dimer, tissue plasminogen activator, antigen, C-reactive protein, and white cell count. The effects were similar in men with and without prevalent cardiovascular disease.
They found that men who had taken up light physical activity in the 20 years since the baseline examination had blood variables similar to those who had exercised for the entire time.
“Lighten up” is the message of a group of researchers who looked at the link between mental stress and dying from a heart-related event. Men whose hearts showed new or worsened wall motion abnormalities during a critiqued 5-minute speech designed to create psychological stress were more likely to die of coronary heart disease in subsequent years than men whose heart did not respond abnormally to the stressor, according to researchers who participated in the Psychological Investigations of Myocardial Ischemia (PIMI) study and the subsequent follow-up that was reported in this week’s issue of Circulation (Circulation. 2002;105:1780–1784).
The researchers, led by David Sheps, MD, of the University of Florida College of Medicine at Gainesville, evaluated 196 patients from the PIMI study who had documented coronary artery disease and exercise-induced ischemia. Between 3.5 years and 5.2 years after the initial physical investigation, the researchers attempted to determine how many of the patients had died. Of the 17 who were dead, the abnormal wall motion had been recorded in 40%, whereas the abnormality was seen in only 19% of the survivors. Ejection fraction, ST-segment depression, and chest pain did not predict mortality.
Although they said that mental stress did increase the risk of mortality from coronary artery disease, the researchers also noted, “The mechanism by which mental stress response increases risk of death is still unclear.” A better understanding of how stress is related to fatal coronary artery events could lead to treatments that would reduce the risk, they concluded.
Genes and Drugs
The drug of choice in treating a particular patient may depend on the individual’s DNA. Diuretics may be the preferred treatment for hypertensive patients who carry a particular genetic mutation of the adducing gene—the Trp460 variant that has been associated with sodium reabsorption and salt-sensitive hypertension—according to researchers from the University of Washington School of Medicine in Seattle and the Leiden University Medical Center in the Netherlands (JAMA. 2002;287:1680–1689).
In another study, researchers at the University of Washington School of Medicine at Seattle, led by Mitchell K. Higashi, PhD, found that the CYP2C9*2 and CYP2C9*3 polymorphisms of the enzyme primarily associated with metabolism of warfarin are associated with an increased risk of over-anticoagulation and of bleeding events among patients in a warfarin anticoagulation clinic setting. Screening for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance techniques to reduce the risk of adverse drug reactions in patients receiving warfarin, the authors noted, although they warned that their study was small and needed further confirmation (JAMA. 2002;287:1690–1698). Further studies will undoubtedly link genetic findings with drug treatment, which promises to be an important new field of clinical endeavor and research in the future.
Want to Avoid Sudden Death? Eat More Fish.
A fast-track article published in the April 4, 2002, issue of the New England Journal of Medicine indicates that long-chain n-3 polunsaturated fatty acids, like those found in fish, have a strong association with a reduced risk of sudden death among men who had no prior evidence of cardiovascular disease (N Engl J Med. 2002;346:1113–1118).
The researchers from the Brigham and Women’s Hospital, Massachusetts General Hospital, and Harvard School of Public Health in Boston, matched 94 participants in the Physicians’ Health Study with no prior evidence of cardiovascular disease (but who had experienced cardiac sudden death) with two controls who were alive and free of confirmed cardiovascular death. They measured the levels of long-chain n-3 fatty acids in samples the physicians had given years earlier that had been carefully stored by researchers. They found that these baseline blood levels of the fatty acids were inversely associated with the risk of sudden death, even when known confounding variables were controlled in the evaluation. For example, men with the fatty acids in the highest quartile had an 81% lower risk of sudden death than men in the lowest quartile.
They wrote, “In summary, taken together with previous data from observational studies and randomized trials, these prospective data suggest that long-chain n¡3 fatty acids found in fish may reduce the risk of sudden death from cardiac causes, even among men without a history of cardiovascular disease. Because >50% of all sudden deaths from cardiac causes occur in people with no history of cardiac disease, preventive efforts must address this segment of the population to have a substantial effect on the overall incidence of sudden death from cardiac causes. If the observed association is causal, increasing the intake of n-3 fatty acids by eating more fish or by taking supplements is an intervention that could be applied to this segment of the population at low cost and little risk.”