Jewish World Review Nov. 8, 2002 / 3 Kislev, 5763

A role for antibiotics in the treatment of vascular disease?

By Robert A. Wascher, M.D., F.A.C.S.

http://www.NewsAndOpinion.com | The bacterium Chlamydia pneumoniae (Cp), a common cause of community-acquired pneumonia, has previously been implicated in the formation of atherosclerotic plaques within the arteries of the neck and legs. Snippets of Cp DNA have previously been recovered from the plaques that narrow diseased arteries, and this has raised concerns that infection with this ubiquitous microorganism might be somehow linked to the development of peripheral vascular disease.

A new study, reported in the current issue of Circulation, looks at the effects of prior infection with Cp, and with treatment using the anti-chlamydial antibiotic roxithromycin, on the progression of preexisting atherosclerosis of the carotid arteries. Initially, a total of 272 patients with carotid artery atherosclerosis (narrowing due to plaque formation on the interior of the artery) were tested for antibodies against Cp (a positive antibody test is evidence of prior infection with Cp).

A total of 123 (45%) of the study patients had positive antibodies against the Cp bacterium. All 272 patients were then followed with serial ultrasound examinations of their carotid arteries for three years. During this 3-year period, the patients who had previously tested positive for antibodies against Cp were noted to develop faster progression of carotid artery narrowing when compared to patients without antibodies against Cp. This finding strongly suggests that CP, while not acting as the sole cause of carotid artery narrowing, may at least be involved in accelerating the process.

A total of 62 patients with positive CP antibodies were subsequently randomized to receive antibiotic treatment over a period of two years in this study, while the remaining antibody-positive patients received a placebo (sugar pill).

All patients were followed with regular ultrasound examinations to assess the thickness of their diseased carotid arteries. The study determined that the 62 patients who tested positive for antibodies against Cp, and who received antibiotics, showed a significant reduction in the rate of progression of carotid artery narrowing when compared to the antibody-positive patients that received the placebo pill. An additional group of 74 patients who took the antibiotic, but who had tested negative for the Cp antibody, showed no improvement in the rate of progression of arterial narrowing when compared to antibody-negative patients receiving the placebo pill.

This study adds compelling evidence that Chlamydia pneumoniae may play an important role in accelerating the growth of atherosclerotic plaques in the arteries of patients with preexisting atherosclerosis. The development of atherosclerotic arterial narrowing is a complex and multifaceted process, and absence of prior Cp infection certainly does not prevent arterial disease and narrowing.

However, Cp infection appears to be an important pathologic cofactor in at least some patients with peripheral vascular disease. A larger study should now be performed, and over a longer duration, to further assess the public health benefit of routinely screening patients with vascular disease for Cp antibodies, and to assess the impact of routinely treating antibody-positive patients with antibiotics.

Such a study might further clarify which subset(s) of patients with vascular disease and antibodies against Cp might benefit the most from the prolonged use of antibiotics. This is important, as the widespread and often indiscriminant use of antibiotics has resulted in the development of bacterial resistance against numerous antibiotics.

Hormone replacement Therapy (HRT) & Alzheimer's Disease

There has been a great deal of controversy regarding HRT for the treatment of the symptoms of menopause over the past 50 years, and particularly since the very large Women's Health Initiative Study released its cautionary results in July of this year.

(Indeed, based upon the enormous confusion that I have observed among both patients and their referring physicians since July of this year, I am currently writing a book that takes an in-depth look at the risks and benefits of HRT based upon scientific research studies.)

There is compelling evidence that the use of HRT for more than a couple of years is linked to an increased risk of breast and uterine cancer, as well as an increased risk of stroke and other cardiovascular diseases. At the same time, Alzheimer's Disease (AD) has been previously noted to occur with increased frequency in postmenopausal women not taking HRT when compared with postmenopausal women taking HRT.

Other studies have shown an apparent link between the loss of natural estrogen production that occurs following menopause and the onset of AD in women. However, the results of these previous studies have not been very conclusive. A new study, reported in this week's issue of the Journal of the American Medical Association (JAMA), adds further fuel to the HRT fire. This prospective study followed 1,357 elderly men (average age of 73 years) and 1,889 women (average age of 75 years) for a period of three years. Among the men, 2.6% developed AD during the study period, while 4.7% of the women developed AD. Among the study volunteers older than 80 years, the incidence of AD was more than twice as high among women as it was among the men.

When the research personnel looked at the influence of HRT on the incidence of AD, they found that a prior history of HRT use cut the risk of developing AD in half among all of the women participating in this study. The longer the duration of HRT, the greater the reduction in the risk of developing AD. Following more than 10 years of HRT, the "excess risk" of AD related to gender (i.e., the difference in rates of AD between age-matched men and women) essentially disappeared.

The use of calcium or vitamin supplements, however, did not appear to offer any protection against AD. Moreover, the AD-reduction benefit of HRT was present only for patients who had a history of prior HRT use. Unless they had taken HRT for 10 or more years, elderly women currently taking HRT appeared to derive no benefit from HRT in terms of AD prevention.

The results of this study will surely add to the debate about the risks and benefits of prolonged HRT, and additional large scale studies will be necessary to evaluate the effects of HRT on breast cancer, uterine cancer, cardiovascular disease and AD in order to obtain a better understanding about the benefits and risks of long-term HRT. There are, in fact, several large HRT studies underway, each looking at the impact of HRT on the risk of AD.

However, it is not known whether or not there is a critical interval in a person's life at which time HRT can favorably affect the aging brain in terms of reducing the risk of AD. The minimum duration of HRT needed to significantly reduce the risk of AD is also not clear, and requires further study in view of other data that confirms a progressively increasing risk of other serious diseases with increasing periods of HRT.

More Good News About Statin Drugs

The current issue of the journal Nature features a very interesting study that looked at the effects of the statin drug atorvastatin (Lipitor) on the development of a multiple sclerosis-like syndrome in mice that are genetically predisposed to this autoimmune disease.

Multiple sclerosis (MS) is a potentially debilitating disease that results when the body's immune system attacks the protective myelin sheath that surrounds nerve cells. Loss of sensation, paralysis and dementia can result from MS, and most treatments are based upon drugs that impair the immune system. The cause (or causes) of MS has been debated for years, but remains unclear at this time.

In the Nature study, the MS-predisposed mice were treated with high doses of atorvastatin, a drug normally used in humans to reduce cholesterol levels. Previous studies of the statin class of drugs have shown that, in addition to directly reducing the liver's synthesis of cholesterol, these drugs are capable of reducing some of the inflammatory factors now thought to be involved in the progression of coronary artery disease.

Other studies have also suggested a possible reduction in the risk of developing Alzheimer's Disease with statin use. In the current study, atorvastatin significantly reduced the development of permanent paralysis in mice experiencing their first attack of MS-related symptoms, while the drug also reversed paralysis in mice experiencing a relapse of established MS.

Even mice with very advanced MS appeared to experience a significant reduction in the severity of paralysis with atorvastatin. The study's authors caution that these striking effects in mice may not necessarily be reproducible in humans, however, as many previous research studies have confirmed.

However, this is a very exciting development with respect to a baffling disease that causes enormous suffering and disability, and for which neither a unifying etiology nor an enduring cure have been found. Other autoimmune disorders that might potentially benefit from statin drugs (in mice, at least!) include rheumatoid arthritis, juvenile diabetes, and lupus. More research needs to be done, of course, and, ultimately, human trials will be needed to confirm that atorvastatin is effective in treating MS in humans as well as in mice.

Briefly....

Journal of the National Cancer Institute: Allium vegetables, which include garlic, onions, chives, leeks and scallions, have been studied extensively for their purported anticancer effects. A study of 238 Chinese men with prostate cancer and 471 men without prostate cancer looked at the relative abundance of allium vegetables in their diets. The men who regularly consumed the greatest amount of allium veggies had about half the risk of developing prostate cancer when compared to the men with the lowest levels of these vegetables in their diets.

This reduction in the risk of prostate cancer was not related to any differences in body weight, intake of other foods, or total caloric intake. Among the men with prostate cancer, a high intake of allium vegetables was also linked with a tendency towards localized prostate cancer, while low allium veggie intake was more common in men with advanced cancer.

New England Journal of Medicine: Despite previous studies that have failed to show any link between the measles, mumps and rubella (MMR) vaccine and autism, rumors of a correlation between the two persist. A study of all children born in Denmark between 1991 and 1998 was performed in order to evaluate the effects of MMR vaccine, if any, on the incidence of autism. Of the 537,303 children born during the study period (representing 2,129,864 "person-years"), 440,655 (82%) received the MMR vaccine.

Among the 537,303 children in the study, 316 developed autism, while an additional 422 were diagnosed with less severe "autistic-spectrum disorders." This large scale study found no significant increase in the risk of autism or "autistic-spectrum disorders" among the children who received the MMR vaccine when compared to the children who did not receive the vaccine. This large population-based study confirms recent research that fails to demonstrate any correlation between the MMR vaccine and the risk of autism or related disorders.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.