Health
Report:
Statins, Diabetes & Stroke
Obesity, GERD & Esophageal Cancer
Statins, Diabetes & Stroke
Obesity, GERD & Esophageal Cancer
By, Robert A. Wascher, MD, FACS
"A critical weekly review of important new research findings for health-conscious readers..."
Last Updated: 1/12/2008
The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician
before making any lifestyle or medication changes, or if you have any
other concerns regarding your health.
STATINS, DIABETES & STROKE
It is difficult to write about the class of drugs known as statins without affecting an almost religious fervor for them amid the growing list of beneficial effects associated with the most commonly prescribed drugs in the United States. The statins were originally developed for their ability to block an enzyme required by the body for the synthesis of cholesterol. Thus, the statins decrease total cholesterol levels in the blood and, additionally, they also specifically reduce LDL (the “bad cholesterol”) levels as well. Numerous clinical research studies have shown that statin drugs reduce the risk of heart disease and heart attacks in patients with elevated cholesterol levels. Additional research has also strongly suggested that statins can also reduce the risk of cardiovascular disease even in patients with normal cholesterol levels. More recently, additional research into the biochemical function of these powerful drugs has also revealed other mechanisms of action in addition to their known effects on cholesterol synthesis and metabolism. One of the most clinically important additional mechanisms of action of statins appears to be their ability to reduce inflammation throughout the body. These anti-inflammatory effects have been linked not only to the statins’ ability to reduce cardiovascular disease, but also to potentially reduce the risk of stroke and, perhaps, some cancers as well. However, the data supporting these additional potential benefits of statins is less well developed than that for cardiovascular disease reduction. I should also stress that not all claims currently being made for statins are likely to turn out to be true, and that, as with all medications, statins have been associated with potentially serious side effects (most notably injury to the liver and muscle tissue). However, it is still difficult to think of any other recently developed class of medications that have accumulated a more profound disease prevention profile than the statins. Two new research studies have added to the already impressive and growing legacy of statin drugs, and suggest an important role for these medications in patients with diabetes, and in the prevention of strokes.
The rising incidence of diabetes mellitus in the developed world parallels the rising incidence of obesity, and not surprisingly. Adult-onset, or Type II, diabetes has long been known to be linked with overeating and obesity. Although diabetes results from a complicated array of genetic and metabolic abnormalities, Type II diabetes fundamentally involves a combination of reduced insulin output from the pancreas and a decreased sensitivity of the body’s cells to insulin. The regulation of glucose (“sugar”) levels in the blood is the results of complex feedback mechanisms between multiple tissues and organs in the body. When glucose levels rise in the blood after a meal, the pancreas is stimulated to increase insulin production and secretion. Insulin, in turn, causes glucose to leave the bloodstream and to enter into the body’s cells, where it can then be utilized to meet the cells’ energy needs. In Type II diabetes, not enough insulin is available from the pancreas, and this overall insulin deficiency is further aggravated by a reduction in the body’s sensitivity and response to insulin. These abnormalities cause the level of glucose in the blood to rise above normal and, over time, a host of diabetes-associated illnesses may result if the disease is not aggressively treated and controlled. Much of the adverse health effects of poorly controlled diabetes revolve around the early onset and progression of atherosclerotic vascular disease. In patients with chronic diabetes, the thickening and ulceration of the lining of critical blood vessels that normally and gradually occurs with aging is accelerated. In particular, smaller caliber blood vessels appear to be preferentially affected in patents with diabetes. In many patients with poorly controlled diabetes, this can eventually result in kidney failure, heart attacks, stroke, blindness, and decreased circulation to the feet and toes. Weight loss, decreasing sugar and carbohydrates in one’s diet, exercise, and (when necessary) medications to control blood glucose levels can all effectively treat most cases of Type II diabetes, and can markedly reduce the risk of diabetes-associated illnesses.
Recently, attention has turned towards the statins and their potential impact on the adverse effects of diabetes. Because of the increased risk of accelerated atherosclerosis in patients with diabetes, there has been great interest in the use of statins to slow down, or even arrest, this pathological process. A new study in the journal The Lancet combined the results from 14 randomized clinical research trials that evaluated the impact of statins on patients with diabetes. Using a statistical method known as meta-analysis, the data from these 14 studies were adjusted and combined in such a way that more powerful scientific deductions could be made (please note, however, that meta-analyses carry their own potential “scientific biases” in their methodology, and are, therefore, far from perfect themselves).
This study analyzed data from almost 19,000 patients with diabetes, and compared them to more than 71,000 patients without diabetes. After following all of these patients for an average of just over 4 years, 3,247 “major vascular events” were observed among the study participants.
Overall, the use of statins was associated with a significant and approximately equal reduction in the risk of death from vascular causes in both the diabetic and non-diabetic patients, and the extent of this reduction in the risk of death was directly proportional to the degree to which LDL levels were reduced after beginning statin therapy. Specifically, this large study appeared to confirm that diabetic patients who received statin drugs had a significantly reduced incidence of heart attack, death due to heart attack, intervention for narrowed coronary arteries, and stroke. Once again, the degree of risk reduction for each of these “adverse vascular events” was directly proportional to the extent of LDL reduction after starting statin therapy in both the diabetic and non-diabetic study volunteers.
The results of this study, when combined with previous research, strongly support the use of statins in patients with diabetes who are at increased risk of developing cardiovascular disease. As a reminder, the use of statins may be associated with serious side effects, and so patients who are placed on these medications must be closely monitored by their prescribing physician.
A second large meta-analysis study, just published in The American Journal of Medicine, evaluated the results of 42 clinical research trials looking at the impact of statin therapy on the risk of death in general, and the risk of stroke, specifically, among more than 121,000 study volunteers. Among the volunteers taking statin drugs, death from any cause was reduced, relatively, by 12%, and the relative risk of stroke was reduced by 16%. As with the previous study, the extent of morality and stroke risk reduction was proportional to the magnitude of LDL reduction achieved after initiation of statin therapy. One caveat derived from this study is that the risk of only so-called “non-hemorrhagic” strokes was reduced by chronic statin therapy. This type of stroke generally results from atherosclerosis of the arteries (in the neck and inside the brain) that supply the brain with blood. The incidence of “hemorrhagic” strokes, which usually result from poorly controlled high blood pressure (or, in some cases, in patients taking blood-thinning medications), was not reduced by statin therapy, however. Additionally, the incidence of fatal strokes was not appreciably altered by statin drugs.
As with prior studies, this large meta-analysis adds to the growing weight of evidence that long-term statin therapy can significantly reduce the risk of life-threatening cardiovascular events.
OBESITY, GERD & ESOPHAGEAL CANCER
While the incidence of cancers of the upper half of the esophagus has been declining in the western world, the incidence of a type of cancer that involves the lower esophagus and upper stomach has been on the rise. A great deal of debate within the medical and scientific communities has yet to clarify the reason(s) for the increasing incidence of adenocarcinoma of the lower esophagus and gastro-esophageal (GE) junction.
A new research study from Australia, just published in the journal Gut, may offer some insight into potential risk factors for this very serious cancer. The authors evaluated almost 800 patients with adenocarcinoma of the esophagus and GE junction, and compared them to 1,580 adults without cancer. This study searched for clinical and lifestyle factors that were more commonly associated with the presence of lower esophageal or GE junction adenocarcinoma and that, therefore, might be considered as risk factors for this type of cancer.
When the two populations of study volunteers were evaluated according to body weight, obesity was identified as a factor that significantly increased the risk of this particular type of cancer. When comparing the heaviest study volunteers with those who had normal height-adjusted body weights, the risk of lower esophageal adenocarcinoma was increased more than 6-fold in the heaviest adults. Obesity also appeared to worsen the risk of this cancer more prominently in men than in women, and in those less than 50 years of age when compared to patients older than 50. When obesity was present in combination with ongoing symptoms of acid reflux (gastro-esophageal reflux, or GERD), the risk of developing adenocarcinoma of the lower esophagus was increased dramatically, to nearly 17 times the risk apparent in non-obese adults without symptoms of GERD. Any degree of obesity, without symptoms of GERD, was associated with a more than 2-fold increase in the risk of this cancer, while symptoms of GERD without attendant obesity was associated with a nearly 6-fold increase in risk. Similar associations were observed with adenocarcinoma of the GE junction, although the magnitude of increased cancer risk associated with obesity and/or GERD was not as great as was observed for adenocarcinoma of the esophagus.
The results of this rather small public health study fit in nicely with the results of previously published studies. Chronic GERD has long been associated with an increased risk for adenocarcinomas of the lower half of the esophagus, and the GE junction. Chronic inflammation of the lining of the lower half of the esophagus is thought, by many experts, to be the primary cause of this highly lethal from of cancer. Obesity, which is itself a risk factor for GERD, has repeatedly been linked to cancers of the esophagus and GE junction by previous studies as well. (Other cancers previously linked to obesity include cancers of the breast, colon, rectum, pancreas, ovary, uterus, prostate and kidney.) The results of this study further suggest that the co-existing combination of obesity and GERD may dramatically increase the risk of esophageal and GE junction adenocarcinoma, and to a much greater degree than the presence of either risk factor alone. The primary limitations of this study are that it evaluated a relatively small population of patients, and as with many epidemiological studies, this is a comparative study that seeks to associate specific findings in one or more groups of patients at a single point in time. (Associating the presence or absence of a disease, at a single point in time, with suspected risk factors for that same disease tends to overestimate the magnitude of the risk factors being studied.)
If you are overweight, then this study provides yet another source of motivation to bring your weight down to within the recommended normal range. Likewise, if you have chronic or frequent heartburn or regurgitation symptoms, or any other symptoms of GERD, you should also seek evaluation and advice from your personal physician.
Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html
Send your feedback to Dr. Wascher at
rwascher@doctorwascher.net
Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
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