Mark of Inflammation
A single test that demonstrates higher than normal levels of serum inflammatory markers—particularly elevated levels of interleukin-6 (IL-6)—was associated with an increased risk of congestive heart failure in elderly people who had not previously had a heart attack, according to researchers from the Framingham Heart Study, Boston University in Boston, Mass, the National Institute on Aging, and the National Heart, Lung and Blood Institute in Bethesda, MD, in a report in this week’s issue of Circulation (Circulation. 2003;107:1486–1491).
The authors led by Ramachandran S. Vasan, MD, of the Framingham Heart Study, investigated the relationship between various serum markers of inflammation in 732 elderly Framingham Study subjects in whom the mean age was 78 years. Approximately two-thirds of the subjects were women and none had previously had a myocardial infarction or congestive heart failure. The serum markers for which the subjects were tested included serum IL-6, C-reactive protein, and spontaneous production of tumor necrosis factor-alpha by peripheral blood monocular cells.
On follow-up that lasted for a mean of 5.2 years, 56 subjects had developed congestive heart failure. When the findings of serum marker tests were evaluated, all findings of elevated serum markers for inflammation were associated with increased risk of congestive heart failure. The authors wrote: “Our findings suggest that elevated inflammatory markers constitute important risk factors for CHF [congestive heart failure] in elderly women and men. Although prior reports have emphasized the importance of inflammation in determining prognosis of people with established CHF, our data suggest that the contribution of inflammatory markers may antedate overt CHF. If confirmed, our observational data raises the possibility of using inflammatory markers to identify patients at high risk for CHF.”
In an accompanying editorial, David R. Murray, MD, of the University of Texas Health Science Center at San Antonio, and Gregory L. Freeman, MD, of the South Texas Veterans Healthcare System, Audie L. Murphy Division, also in San Antonio, wrote: “The result of this study must be interpreted with caution. The study population consisted of predominantly elderly, white subjects (67% female) with a high prevalence of hypertension (≈70%), atrial fibrillation (≈7%), and pre-existing cardiovascular disease (≈25% with history of angina, cerebrovascular or peripheral vascular disease without prior documented MI [myocardial infarction]). As pointed out by the authors, the results cannot be generalized to include other ethnicities, younger age groups, and patients with different co-existing conditions.”
They were even more concerned because the researchers had not documented the status of ventricular function at the beginning of the study. “Surely some of these patients must have had subclinical LV [left ventricular] systolic and/or diastolic dysfunction at the time of cytokine assessment, related to occult MI, myocardial hibernation, pressure or volume overload, or other forms of injury,” they noted.
Because of that, they wrote, the authors cannot firmly state whether the inflammatory markers predicted disease or were simply evidence of undiagnosed problems. “The study does, however, offer some clues suggesting that inflammatory mediators can predict a transition towards a congested state,” they wrote. “This study does not define whether inflammatory markers predict the development of ‘noncongestive’ heart failure.”
Whither Hormone Replacement Therapy?
A new study of the combination of estrogen-progestin (Prempro) used as hormone replacement therapy in menopausal women shows that the combination has no positive effect on measures of quality of life related to health, according to researchers from the federally funded Women’s Health Initiative in a reported released online by The New England Journal of Medicine on March 17, 2003 (N Engl J Med. 2003;10.1056/NEJMoa03031).
The report, authored by all the researchers involved in the Women’s Health Initiative and led by Jennifer Hays, PhD, of Baylor College of Medicine, in Houston, Tex, noted that although a previous report in the Journal of the American Medical Association (JAMA. 2002;288:321–333) had already indicated the significant health risks associated with estrogen and progestin as hormone replacement therapy, little was understood about the effect of the combination on the quality of life of menopausal women.
In this analysis of quality of life measures made at the beginning of the study and after one year in the 16 608 women who were randomly assigned to hormone replacement therapy or placebo and after three years in a 1511-women subset, the researchers found that the combination of hormones had no significant effect on general health, vitality, mental health, symptoms of depression or sexual satisfaction. It was found that the combination had a small but statistically meaningful effect on sleep disturbance, physical functioning, and body pain after one year of treatment. The researchers reported that the mean benefit in terms of sleep disturbance was 0.4 points on a 20-point scale; in terms of physical functioning, it was 0.8 points on a 100-point scale; in terms of pain, 1.9 points on a 100-point scale. There was no benefit found after 3 years. “Among women 50 to 54 years of age with moderate-to-severe vasomotor symptoms at base line, estrogen and progestin improved vasomotor symptoms and resulted in a small benefit in terms of sleep disturbance but no benefit in terms of the other quality-of-life outcomes,” the researchers noted.
In an accompanying perspective on the study (JAMA. 2003;348:10.1056/NEJMpo30038), Denise Grady, MD, MPH, of the University of California at San Francisco, wrote: “Postmenopausal therapy with estrogen and progestin results in increased risks of disease, does not make asymptomatic women feel better, and does not improve cognition. There is no role for hormone therapy in the treatment of women without menopausal symptoms. Women with vasomotor symptoms must weigh the risks associated with treatment against the benefit of symptom relief. Vasomotor symptoms occur in about two thirds of women and are very distressing in 10 to 20 percent. We clearly need to identify new treatments that are highly effective and safe.”
Ironically, on March 13, 2003, the US Food and Drug Administration (FDA) announced approval of a lower dose of Prempro, the form of estrogen-progestin tested in the Women’s Health Initiative. The new form of the drug contained 0.45 estrogen and 1.5 progestin “to treat specific symptoms of menopause,” according to the FDA release.
The FDA release further noted: “Prempro is effective for treating moderate to severe symptoms of hot flashes and night sweats and is indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy (burning, itching, and dryness in and around the vagina). However, topical vaginal products should be considered when being prescribed solely for the treatment of symptoms of vulvar and vaginal atrophy. The new lower dose will provide an additional option for postmenopausal women. FDA continues to advise women to talk to their doctors and, if they decide that estrogen and progestin containing products are appropriate, they should use the lowest dose for the shortest duration to reach treatment goals.”
Dangerous New Ailment Prompts Emergency Travel Advisory From the World Health Organization
In a highly unusual move, the World Health Organization on March 15, 2003, issued a worldwide emergency travel guidance to travelers and airlines concerning a new disorder called severe acute respiratory syndrome (SARS) reported in Canada and eastern Asia.
“This syndrome, SARS, is now a worldwide health threat,” said Gro Harlem Brundtland, MD, Director General of the World Health Organization. “The world needs to work together to find its cause, cure the sick, and stop its spread.”
The warning from the WHO does not recommend that people avoid or restrict travel but does advise travelers to be aware of the main symptoms of the disorder, including high fever and one or more respiratory symptoms such as cough, shortness of breath, and difficulty breathing. In addition, they should be aware if they have had close contact with a person diagnosed with the new syndrome. If this occurs, then the traveler should seek immediate medical attention and request that their illness be reported to public health authorities as well as the health care personnel treating them.
In the week before the warning, 150 suspected cases of the disease were reported to public health authorities around the world. The reports came from Canada, China, Hong Kong, Indonesia, the Philippines, Singapore, Thailand, and Vietnam. On March 15, 2003, a passenger who was ill and companions who had traveled from New York City and landed in Frankfurt, Germany, were removed from their flight and isolated in a nearby hospital.
Public health officials have not yet identified the organism or agent associated and they have too little information from which to provide recommendations on avoiding the infection.