Aspirin & the Risk of Colorectal Polyps

Recent studies have linked the use of COX-2-specific anti-inflammatory medications with a decreased risk of colorectal polyps and cancers. However, this class of drugs is rather expensive, and there is some evidence that they lack the cardiovascular protective effect of aspirin. Aspirin blocks all of the forms of the COX enzyme, including the form (COX-1) that increases the ability of blood to develop blood clots.

In this week's New England Journal of Medicine is a randomized double-blind study that looked at the ability of aspirin to reduce the risk of colorectal adenomas (polyps) in volunteer research subjects who had previously been diagnosed with colorectal cancer. These patients were selected for this study because their prior history of colorectal cancer placed them at increased risk of developing future benign and malignant colorectal polyps. It is thought that nearly all colorectal cancers begin as adenomatous polyps, and that cumulative genetic mutations cause some of these polyps to degenerate into cancerous tumors. Therefore, any intervention that reduces the risk of developing colorectal adenomas should also reduce the risk of colorectal cancer.

In this study, half of the volunteers were given a 325 mg aspirin tablet each day, while the remaining volunteers received a placebo (sugar pill). The study was actually prematurely halted when an interim review noted a significant reduction in the incidence of colorectal polyps among the volunteer patients taking the daily aspirin tablet.

Among the 517 volunteers in the study who had undergone colonoscopy prior to the study's termination, 17% of the patients taking aspirin had at least one colorectal adenoma, while 27% of the volunteers taking the placebo had adenomas. Not only were the volunteers in the aspirin-taking group less likely to have adenomatous polyps, but those who did have polyps actually had, on the average, fewer polyps than the placebo-group volunteers who also developed polyps. The authors concluded that taking one 325 mg aspirin tablet per day appeared to reduce the risk of colorectal adenomas by 35% in a group of patients with a prior history of colorectal cancer.

One note of caution, aspirin can cause serious and, rarely, life-threatening side effects. So, please check with your doctor before initiating daily aspirin therapy!

BABY ASPIRIN & THE RISK OF COLORECTAL ADENOMAS

A second study of aspirin on the risk of colorectal adenomas is also featured in the current issue of the New England Journal of Medicine. In this randomized double-blind study, 1,121 volunteers with a recent history of colorectal adenomas were randomized to receive a daily 81 mg "baby" aspirin tablet, a 325 mg "adult" aspirin tablet, or a placebo pill. All patients underwent colonoscopy at the beginning of the study, and were scheduled to undergo follow-up colonoscopy 3 years later. Indeed, 97% of the study patients did undergo colonoscopy according to the study's protocol.

In these high-risk patients, 47% of the placebo-group volunteers developed additional colorectal adenomas during the study. The group taking 81 mg of aspirin per day had a 38% incidence of additional polyps, while the volunteers taking 325 mg per of aspirin per day had a 45% incidence of polyps. When considering only cancerous and pre-cancerous polyps, 81 mg of aspirin per day reduced the risk of developing such high-risk polyps by 41%, while 325 mg of aspirin today reduced the risk of such lesions by 17%.

While the counterintuitive effect of daily aspirin dose on adenoma development noted in this study is difficult to explain, this study (and the previously cited study, above) suggest that plain old aspirin may help reduce the risk of developing colorectal adenomatous polyps and cancers while, at the same time, reducing the risk of heart attacks and stroke. There are few medications in the world that offer such an impressive array of protective effects, and at such a small cost.

UPDATE: DAILY MULTIVITAMIN & MINERALS SUPPLEMENTS

We live in a vitamin and supplement crazed society (yours truly included, I might add). However, the majority of such supplements sold in the United States have little-and often no-scientific data to support their use. Indeed, the Food & Drug Administration (FDA) requires prescription drug manufacturers to not only demonstrate the purity and potency of their products, but also to prove their efficacy and safety as well. The rules for manufacturers of vitamins and supplements require only that such products be manufactured under hygienically sound conditions, and that the supplements have not been previously found by the FDA to be harmful. Efficacy, side effects profiles and potency are not issues of concern to the FDA when it comes to the burgeoning vitamin and supplements industry.

With this background in mind, an interesting little study in the current issue of the Annals of Internal Medicine looked at the impact of daily multivitamin and mineral supplementation on the risks of infection among 130 adult volunteers over the course of 1 year. Volunteers were randomized to receive either the supplement pills or placebo pills. The study found that 73% of the placebo-group volunteers reported an infectious illness over the course of the study, while only 43% of the group receiving supplements experienced such illnesses.

When the study looked at volunteer patients with adult-onset diabetes, the difference was even more striking. A total of 93% of the diabetics that received placebo pills reported an episode of an infectious ailment during the study, while only 17% of the diabetics who received the supplements reported such events. The authors concluded that daily multivitamin and mineral supplementation reduces the risk of infectious illnesses, particularly among patients with type II (adult-onset) diabetes. This is a rather important finding, as diabetics are more easily predisposed to developing infections than those without diabetes. This relatively small study should be followed-up with a much larger scale study in order to confirm these findings.

MORE BAD NEWS ABOUT C-REACTIVE PROTEIN

Any regular reader of this column knows that C-reactive protein (CRP) has been increasingly implicated as a key risk factor for cardiovascular disease and heart attack. This important mediator of inflammation has recently been found to be more predictive of heart attack risk than the more commonly used cholesterol blood tests. Now, a new study in the journal Circulation looks at the levels of CRP in the blood of patients with asymptomatic abdominal aortic aneurysms (AAA).

The aorta is the largest artery in the body, and arises directly from the heart, coursing through the chest, and then down through the abdomen. The wall of the aorta can become progressively weakened by atherosclerosis and inflammation, until it becomes dangerously thinned-out. As the aortic wall continues to weaken, it begins to dilate, forming an AAA. When the diameter of an AAA reaches about 5 cm (about 2 inches), the risk of aortic rupture begins to climb. As the AAA grows larger, so too does the risk of rupture.

In this study, 39 patients with AAA had blood levels of CRP tested, while CRP levels in the AAA tissue of 16 patients who underwent surgical repair of their aneurysms were also assessed. The study found that the amount of CRP in the blood was proportional to the size of the AAA, with higher levels of CRP being associated with increasing AAA diameter. In 25% of the 16 AAA tissue samples, CRP was identified within the walls of the diseased aorta.

This is the first report that has studied the relationship between CRP and AAA, and adds further weight to the theory that atherosclerosis, whether occurring in the coronary arteries of patients with coronary artery disease, or in the ballooned-out aortas of patients with AAA, is mediated by inflammation in general, and CRP in particular.

ORAL HEALTH & THE RISK OF CARDIOVASCULAR DISEASE

In another angle on the role of inflammation in the development of cardiovascular disease, a second study published in Circulation looked at the relationship between poor oral health and arterial disease. Previous studies have linked tooth loss and periodontal disease to an increased risk of heart disease and stroke. However, the current study looked specifically at the impact of poor oral health on the arteries that feed the legs and feet. A total of 45,126 male health professionals, all without a history of cardiovascular disease, were enrolled into the study. The study volunteers were then followed for a period of at least 12 years, during which time 342 study patients developed peripheral arterial disease (PAD).

The study found that cumulative tooth loss was significantly associated with a higher risk of developing PAD. Patients with chronic periodontal disease were 41% more likely to develop PAD than patients with healthy gums, even after controlling for other known cardiovascular disease risk factors among all of the study patients. Moreover, tooth loss due to periodontal gum disease within the previous 2 to 6 years was most strongly associated with the development of PAD. This study, therefore, adds more evidence to support the theory that chronic oral inflammation may have an adverse effect of the body's arteries, including the arteries that supply the heart, the brain, and the lower extremities. Have you see your dentist this year...?

MORE DATA ON HORMONE REPLACEMENT THERAPY & THE RISK OF BREAST CANCER

Several large scale studies have been published over the past year, linking chronic postmenopausal hormone replacement therapy (HRT) with an increase in the risk of breast cancer. The highest risk has been found among women who have been prescribed combined progestin and estrogen HRT, although several studies indicate that estrogen alone also appears to increase the risk of breast cancer. In most women taking HRT, a progestin hormone is added to the estrogen hormone in order to reduce the risk of estrogen-induced uterine cancer. Most women who have previously undergone hysterectomy are prescribed an estrogen alone, or "unopposed estrogen," as HRT.

A new study, just published in the journal Cancer, looked at the HRT habits of 29,508 women, all of whom were interviewed during the 1990-1992 timeframe. The women were again surveyed in December of 2001, and the incidence of breast cancer in this group of women was then correlated with their history of HRT use.

When compared to women who had used no HRT, the women who had taken the combined progestin & estrogen HRT had nearly 5 times the risk of developing breast cancer during the course of this study, with the highest risk occurring after more than 48 months of continuous combination HRT use. In this study, the use of estrogen alone did not appear to increase the risk of breast cancer, at least during the study period. In women who stopped HRT during the course of the study, there was no further increase in breast cancer risk after 5 years of non-use.

Based upon these findings, the study's authors estimate that women who use combined HRT for at least 48 continuous months will experience, over a period of 10 years, a predicted 7% incidence of breast cancer, compared to a 2% risk among women who have not used any HRT. To put this into context, this increased risk following continuous combination HRT use for at least 48 months is about half of the increased risk that has been attributed to carriers of the BRCA1 gene mutation.

Although the effects of unopposed estrogen HRT on the risk of breast cancer remains somewhat unclear at this time, there is mounting-and solid-evidence that combined HRT increases the risk of breast cancer, as well as the risk of heart disease, blood clots and stroke. Once again, my recommendation is that women attempt to gradually eliminate-or at least minimize-their use of HRT, and combined HRT in particular, after reaching menopause. There are other effective drugs available to reduce the risk of osteoporosis, mood changes and temperature intolerance. You should, of course, check with your gynecologist or family physician before starting or stopping HRT.

Dr. Robert A. Wascher