The Genetic Factor
Genetic factors play a significant role in the quantity of coronary artery calcification (CAC) found by electron beam computed tomography, according to researchers from the Mayo Clinic in Rochester, Minn, the Windber Research Institute in Windber, Pa, and The University of Texas Health Science Center in Houston, in a report in this week’s issue of Circulation (Circulation. 2002;106:304–308).
In the study, led by Patricia A. Peyser, PhD, of the Department of Epidemiology at the University of Michigan in Ann Arbor, researchers noted that although CAC quantity predicts future coronary heart problems, the measurable risk factors explain <50% of the variability in coronary artery calcification. To determine the factors that contribute to CAC, they quantified the contributions of known risk factors and genetic influences on the calcification quantity found in 698 asymptomatic adults.
They adjusted their calculations for age, sex, fasting glucose, systolic blood pressure, years of smoking (by pack), and low-density lipoprotein cholesterol, and found that 41.8% of the residual variation in CAC quantity could be attributed to genetic factors. “Our findings suggest a substantial genetic component for subclinical coronary atherosclerosis variation as measured by CAC quantity,” they concluded, “even after accounting for effects of genes acting through some measured atherosclerosis risk factors. Although the CAC quantity process has a complex pathogenesis that likely is influenced by the interaction of numerous environmental and genetic factors, the evidence for genetic effects suggests it should be possible to localize previously unknown genes that influence CAC on quantity.”
How Much Can Statins Do?
A landmark study published in the July 6, 2002, issue of The Lancet (Lancet. 2002;360:7–22) demonstrates the value of statins in reducing the risk of heart attack and stroke in patients with diabetes, arterial disease, or previous stroke. Statins (in this case simvastatin) benefited even patients in those categories who were believed to have normal or even low levels of cholesterol.
Called the Heart Protection Study and led by Rory Collins from the University of Oxford’s Clinical Trial Service Unit, the study enrolled 20 536 adults with coronary disease, as well as other diseases involving occluded arteries and diabetes. The subjects were randomly assigned to receive either 40 mg of simvastatin daily or a placebo. Treatment resulted in a lower low-density lipoprotein level of 1.0 mmol/L in the treatment group.
The treatment group demonstrated a reduced all-cause mortality rate with only 12.9% among the treatment group versus 14.7% among those who took placebos. The greatest factor in the reduction in all-cause mortality was the reduced coronary death rate in the treatment group (5.7% versus 6.9% in the placebo group). There was a marginally significant reduction in other vascular deaths and a nonsignificant reduction in nonvascular deaths, according to the authors, who concluded that 5 years of simvastatin could prevent major vascular events in 70 to 100 people per 1000.
“HPS (Heart Protection Study) shows unequivocally that statins can produce substantial benefit in a very much wider range of high-risk people that had been previously thought,” Dr Collins said. “These new findings are relevant to the treatment of some hundreds of millions of people worldwide. If now, as a result, an extra 10 million high-risk people were to go on statin treatment, this would save about 50 000 lives a year—that’s a thousand each week. In addition, this would prevent similar numbers of people from suffering nonfatal heart attack or stroke.”
Malpractice Premiums at “Crisis” Levels
The high cost of malpractice premiums is reaching crisis levels in ≤12 states, according to new information from the American Medical Association (AMA). In ≤30 other states, members of high-risk specialties such obstetrics and gynecology are considering leaving their practices, according to an AMA report released June 17, 2002 (available at: http://www.ama-assn.org/ama/pub/article/1616-6373.html).
After the group analyzed liability rates in the 50 states, President Richard F. Corlin, MD, announced at a news conference that, “Doctors are disappearing from America’s communities on a regular basis because of skyrocketing medical liability insurance premiums and an out-of-control legal system. As insurance becomes unaffordable or unavailable, and the legal system produces multi-million dollar jury awards on a regular basis, physicians are forced to limit services, leave their practice, or relocate—all of which seriously impede patient access to high-quality health care.”
The AMA analysis found that the crisis was most severe in Florida, Georgia, Mississippi, Nevada, New Jersey, New York, Ohio, Oregon, Pennsylvania, Texas, Washington, and West Virginia.
Dr Corlin and representatives from several crisis states and specialty societies called on physicians, patients, and elected officials to pass medical liability reform in their state legislatures and to support H.R. 4600—the HEALTH Act of 2002, a bipartisan bill recently introduced in Congress and supported by >40 medical societies and patient advocacy organizations.
Women’s Health Initiative Stops Trial of Estrogen-Progestin, Saying Risks Outweigh the Benefits
The data safety and monitoring board for the Women’s Health Initiative (WHI) pulled the plug on the estrogen-progestin portion of the large study in early July, saying that the overall risks of the trial outweighed any benefits. Of particular concern were increased risks of vascular disease and breast cancer, the researchers said in a released statement. The report of the trial appeared on JAMA-Express, the web version of the Journal of the American Medical Association, on July 9, 2002, and will appear in the July 17 print issue (JAMA. 2002;288:321–333).
“We have long sought the answer to the question: Does postmenopausal hormone therapy prevent heart disease and, if it does, what are the risks?” asked Claude Lenfant, MD, Director of the National Heart, Lung, and Blood Institute, which sponsored the trial. “The bottom-line answer from the WHI is that this combined form of hormone therapy is unlikely to benefit the heart. The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits—and a 26% increase in breast cancer risk is too high a price to pay, even if there were a heart benefit. Similarly, the risks outweigh the benefits of fewer hip fractures. Menopausal women who might have been candidates for estrogen plus progestin should now focus on well-proven treatments to reduce the risk of cardiovascular disease, including measures to prevent and control high blood pressure, high blood cholesterol, and obesity. This effort could not be more important: Heart disease remains the number one killer of American women.”
Letters were sent to 16 608 participants in the trial advising them to stop taking their pills immediately. The women were aged 50 to 79 years and had an intact uterus. Approximately half the women were taking the hormone combination and the other half was taking placebo.
The study reported that women who took the estrogen-progestin combination had a:
41% increase in strokes
29% increase in heart attacks
50% increase in venous blood clots
22% increase in total cardiovascular disease
26% increase in breast cancer
37% percent reduction in colorectal cancer
33% reduction in hip fracture rates
24% reduction in total fractures
The study provides women who had long been unsure about the risks and benefits of hormone replacement therapy with information that can help them make their choice, along with the advice of their physician.
“Women with a uterus who are currently taking estrogen plus progestin should have a serious talk with their doctor to see if they should continue it. If they are taking this hormone combination for short-term relief of symptoms, it may be reasonable to continue since the benefits are likely to outweigh the risks. Longer term use or use for disease prevention must be reevaluated given the multiple adverse effects noted in WHI,” said Jacques Rossouw, MD, Acting Director of the Women’s Health Initiative.
Other studies that are part of the Women’s Health Initiative will continue with careful monitoring by the Data Safety and Monitoring Board. One study of estrogen treatment alone in women who do not have uterus continues, as do studies of low-fat eating patterns and calcium/vitamin D supplementation. The Women’s Health Initiative is sponsored by the NHLBI along with the National Cancer Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, and the Office of Research on Women’s Health. Wyeth-Ayerst provided medication for the estrogen plus progestin study.