THURSDAY, May 8 (HealthDay News) -- That unusual, harsh sound a doctor can hear when passing a stethoscope over a main artery to the brain could indicate an increased risk of heart attack and death from heart disease and stroke, a new study finds.

The sound -- called a carotid bruit (pronounced brew-ee) -- is caused by turbulent blood flow due to buildup of fatty deposits in one of the two arteries that carry blood to the front and middle part of the brain. It is usually regarded as a possible indicator of increased risk of stroke.

Now an analysis of 22 studies finds that people with carotid bruits are more than twice as likely to have heart attacks or to die of cardiovascular disease. "The presence of a carotid bruit should heighten clinician concern for coronary heart disease," said the report by physicians at Walter Reed Army Medical Center in Washington, D.C.

The studies included 17,295 people who were followed for an average of four years. "In the four studies in which direct comparison of patients with and without bruits were possible, the odds ratio for myocardial infarction [heart attack] was 2.15 and for cardiovascular death 2.27," the report said.

The findings are published in the May 10 issue of The Lancet.

Using the presence of a bruit as an indicator of cardiovascular risk could be helpful, but "there are some unresolved questions about the usefulness of carotid bruit and prognosis," said Dr. Victor Aboyans, a cardiologist at Dupuytren University Hospital in Limoges, France, and co-author of an accompanying editorial in the journal.

"First, many of the patients who were studied already had cardiovascular disease, so what is the additional value of carotid bruit in such a case?" Aboyans asked. "The second issue is that some patients who don't have carotid bruit may have other evidence of cardiovascular disease."

Several studies have shown that starting preventive measures for stroke on the basis of screening for carotid bruit aren't useful, Aboyans said. Nevertheless, presence of carotid bruit could prompt physicians to be more aggressive in recommending measures to reduce the risk of cardiovascular disease, such as cholesterol reduction, he said.

Dr. Deepak Bhatt, associate director of the Cleveland Clinic Cardiovascular Coordinating Center, said, "The [study authors'] recommendation that they be even more aggressive with risk modification, that is good clinical judgment."

Physicians routinely listen for possible carotid bruits when doing a physical examination of people who are middle-aged or older, Bhatt noted.

Studies have shown that there's a link between the risk of stroke and of coronary heart disease, Bhatt said. "The core knowledge already exists," he said. "This study helps put a number on how high the risk is."

But the study raises some practical issues, Bhatt added. "One is whether, if a carotid bruit is found, to go ahead and do an ultrasound examination," he said. "I would say yes, but it is controversial. The U.S. Preventive Task Force recommends against routine ultrasound in general."

More information

Learn what a carotid bruit is and what it might mean from the American Heart Association.

The latest findings from the Multiethnic Study of Atherosclerosis (MESA) are believed to provide the first large scale of evidence of such a link and give the estimated 72 million obese American adults another reason to change their lifestyle.

"The biological effects of obesity on the heart are profound. Even if obese people feel otherwise healthy, there are measurable and early chemical signs of damage to their heart, beyond the well-known implications for diabetes and high blood pressure," senior study investigator Dr. Joao Lima, a professor of medicine and radiology at the Johns Hopkins University School of Medicine and its Heart Institute, said in a prepared statement.

There is "now even more reason for (obese people) to lose weight, increase their physical activity and improve their eating habits," Lima said.

He and his colleagues tracked the development of heart failure in an ethnically diverse group of nearly 7,000 people, ages 45 to 84, who enrolled in the MESA study, starting in 2000. Of the 79 participants who've developed congestive heart failure so far, 35 (44 percent) were physically obese (body mass index of 30 or greater).

On average, obese participants were found to have higher blood levels of key immune system proteins involved in inflammation (interleukin 6, C-reactive protein, and fibrinogen) than non-obese participants. A near doubling of average interleukin 6 levels alone was associated with an 84 percent increased risk of heart failure.

"Our results showed that when the effects of other known disease risk factors -- including race, age, sex, diabetes, high blood pressure, smoking, family history and blood cholesterol levels -- were statistically removed from the analysis, inflammatory chemicals in the blood of obese participants stood out as key predictors of who got heart failure," Lima said.

He added that doctors "need to monitor their obese patients for early signs of inflammation in the heart and to use this information in determining how aggressively to treat the condition."

Lima and colleagues also found a link between inflammation and metabolic syndrome, which doubles a person's chances of developing heart failure. Metabolic syndrome is a collection of risk factors -- obesity, high blood pressure, elevated blood glucose levels, excess abdominal fat, and abnormal cholesterol levels -- that increase the risk of heart disease and diabetes.

The study was published in the May 6 issue of the Journal of the American College of Cardiology. The MESA study was expected to continue tracking patients through 2012.

More information

The American Heart Association has more about heart failure.

The risks of dying from other conditions also decline after quitting, although the time frame varies depending on the disease.

"The harms of smoking are reversible and can decline to the level of nonsmokers," said study author Stacey Kenfield, whose report is in the May 7 issue of the Journal of the American Medical Association. "For some conditions like chronic obstructive pulmonary disease, it can take more than 20 years, but there is a rapid reduction for others."

"It's never too early to stop, and it's never too late to stop," added Kenfield, who is a postdoctoral research fellow in the department of epidemiology at the Harvard School of Public Health in Boston.

Smoking is still the leading preventable cause of death in the United States. Not only does tobacco smoke cause lung cancer, it is also implicated in heart disease, other cancers and respiratory diseases.

According to the World Health Organization, an estimated 3 million people in industrialized countries will have died as a result of tobacco use by 2030, and an additional 7 million people in developing countries face the same fate.

This research is a continued follow-up on the Nurses' Health Study, a large trial involving more than 100,000 women. Scientists now have 22 years of data on the participants.

Current smokers had almost triple the risk of overall death compared with women who had never smoked.

Current smokers also had a 63 percent increased risk for colon cancer compared with never-smokers, while former smokers had a 23 percent increased risk. There was no significant association between smoking and ovarian cancer.

And women who started smoking earlier in life were at a higher risk for overall mortality, of dying from respiratory disease and from any smoking-related disease.

However, a smoker's overall risk of dying returned to the level of a never-smoker 20 years after quitting. The overall risk declined 13 percent within the first five years of abstaining.

Most of the excess risk of dying from coronary heart disease vanished within five years of quitting.

For chronic obstructive pulmonary disease, the return to normal took almost 20 years, although there was an 18 percent reduction in the risk of death seen within five to 10 years after quitting.

And the risk for lung cancer didn't return to normal for 30 years after quitting, although there was a 21 percent reduction in risk within the first five years compared with women who continued to smoke.

Many previous studies on tobacco use had focused on men and on lung cancer, the authors stated. They also only looked at smoking status at the beginning of the study. "We got smoking information every two years, so we feel we have a more accurate estimate of current and past smoking," Kenfield said. "We saw increased risks for current smokers [than previous studies], and we think that's because we know who the current smokers are."

"This shows the power of quitting smoking," said Dr. Jay Brooks, chairman of hematology/oncology at Ochsner Health System in Baton Rouge, La. "We've known this for a number of years, but the beauty of this study is it is a very large and well-studied group of people. When I tell people to quit smoking, I say the effect of the heart precedes that of the lungs. If you've smoked, you need to be cognizant that you're still at an increased risk of lung cancer."

More information

Visit the American Lung Association for more on women and smoking.

MONDAY, May 5 (HealthDay News) -- The anti-clotting drug cilostazol is as good as aspirin at preventing recurrent stroke and it causes less bleeding in the brain, a study by researchers at Peking University First Hospital in Beijing shows.

The trial included 360 patients stroke patients who took cilostazol for 12 to 18 months and 359 patients who took aspirin for the same length of time. Twelve patients in the cilostazol group and 20 patients in the aspirin group suffered recurrent stroke.

The researchers calculated that cilostazol reduced the risk of recurrent stroke by 38 percent, which is not statistically significant. But they also found that far fewer brain bleeding events occurred in the cilostazol group (one patient) than in the aspirin group (seven patients), which was statistically significant.

"The lower rates of ischemic and hemorrhagic stroke in the cilostazol group suggests that cilostazol might be a more effective and safer alternative to aspirin for Chinese patients with ischemic stroke; however, a larger phase III trial is required to confirm this," the researchers wrote.

Stroke is the second leading cause of death in China. While aspirin is effective for preventing recurrent stroke, Asian people are more likely than others to suffer brain bleeding when taking aspirin, and the incidence of such bleeds in China is higher than in high-income nations. Cilostazol works through a different mechanism than aspirin.

The study appears online Monday in The Lancet Neurology, and will be published in the June print edition of the journal.

"The implications of these results for clinicians are that they offer hope for a safer antiplatelet [anti-clotting] drug that is at least as effective as aspirin for use in patients with ischemic stroke," Dr. Graeme J. Hankey, department of neurology, Royal Perth Hospital in Australia, wrote in an accompanying editorial.

More information

The American Stroke Association outlines ways to prevent another stroke.

The studies identify "new genes that are of potential importance for either the treatment of cardiovascular disease or potentially screening individuals who may be at higher risk of developing cardiovascular disease," said Dr. Alexander Reiner, of the University of Washington, Seattle, who authored one of the reports.

Still unresolved, however, is the exact nature of the relationship between C-reactive protein (CRP) levels and cardiovascular disease.

"That's an absolutely crucial piece of evidence that we don't have, and until we have it, we cannot know whether any of these new [genetic variants] will predict disease," said Dr. James Scott of Imperial College London, who was not involved in either study.

The reports are published in the May issue of The American Journal of Human Genetics.

Researchers have known for some time that blood CRP levels can predict one's risk of heart disease and stroke. Like the swelling that occurs when someone cuts a finger, cardiovascular disease is, to a large extent, an inflammatory condition. CRP is an indicator of that inflammation. Not surprisingly, environmental risk factors such as smoking, diet and exercise strongly influence CRP levels. But genetics also play a role -- accounting for about 40 percent elevated CRP levels, Reiner said.

"The genetic side of this is rather straightforward," explained Dr. Paul Ridker of Harvard Medical School and Brigham and Women's Hospital in Boston, who led the second study. "If we know people with high CRP levels are at risk, what governs CRP levels? There's a high environmental risk -- people who don't exercise, who smoke, who are overweight, tend to have higher CRP levels than thin, athletic people. But some thin, athletic people have high CRP levels anyway."

Some genetic factors (including variants in the CRP gene itself) had already been identified. But they accounted for only a small percentage of the variance in these levels; researchers wanted to find the other players. In separate efforts, Reiner and Ridker led research teams to see if they could locate them.

Using genetic material and data stemming from three separate cardiovascular studies that comprised more than 12,000 individuals, the groups scanned for genetic differences that correlated with elevated CRP levels. Their tools were DNA microarrays -- glass slides, about the length and width of a stick of gum, which can probe more than 300,000 individual genetic variants per individual. Reiner's team also employed a candidate gene approach, looking specifically at polymorphisms in specific genes the scientists thought might play a role.

The teams found seven genomic regions that appeared to be strongly correlated with CRP levels. Six of those regions contained genes associated in one way or another with metabolic syndrome; the seventh contained no known genes. These six genomic locations read like a Who's Who of cardiovascular disease and metabolic disorder, genes such as HNF1A, which regulates the CRP gene; the leptin receptor, which regulates weight; a regulator of glucose metabolism; and apolipoprotein E.

"I think it's quite interesting that genes involved with traits of metabolic syndrome are also associated with CRP," said Dr. Caroline Fox, medical officer of the National Heart, Lung, and Blood Institute. "I think that's the most fascinating aspect of this paper."

"From our perspective, it's an incredibly satisfying finding," said Ridker. "Often when you do genome-wide association studies, you get genes that you don't understand. In this case, we found a gene cluster that makes perfect sense."

Scott, who has performed similar (albeit unpublished) analyses, said he believed the findings. "We basically replicate all of those loci, the headline loci anyways," he said. "I'm sure it's right, absolutely."

According to Ridker, "The 'Aha' moment was recognizing that these six or seven genes are all interrelated to these metabolic pathways. The question is, I know CRP predicts heart attack and stroke, and these genes are related to CRP. Do these provide clues to what the proper interventions might be? And we think the answer is yes."

Indeed, given the link between CRP and cardiovascular disease, researchers have instigated clinical trials to determine whether individuals with elevated CRP levels, but low cholesterol, should be treated proactively. Ridker heads one of those trials, called JUPITER, which involves the use of a cholesterol-lowering statin called Crestor. On March 31, AstraZeneca announced it was closing JUPITER, "because there is unequivocal evidence of a reduction in cardiovascular morbidity and mortality amongst patients who received CRESTOR when compared to placebo."

But Scott cautioned that fundamental questions must be addressed before any drugs or therapies targeting the loci identified in these two studies can be developed.

"Is it [CRP] merely a response to inflammation, or does it make the inflammation worse?" he asked. "Until that question is addressed, these genes are not a valid drug target."

Metabolic syndrome comprises a collection of risk factors that often lead to cardiovascular disease, including abdominal obesity, elevated blood sugar, elevated blood pressure and abnormal lipids, said Fox. According to the American Heart Association, the syndrome affects almost 50 million Americans.

More information

For more on metabolic syndrome, visit the American Heart Association.