The study is the first to identify common genetic variants influencing stroke risk in the United States and may lead to better treatments, they reported on Wednesday.

While other stroke-related genes have been discovered, none involved such a wide portion of the population, said Eric Boerwinkle of The University of Texas Health Science Center.

“This is a first step in unraveling the genetic contributions of this debilitating disease,” said Boerwinkle, whose team was one of several contributing to the study published in the New England Journal of Medicine.

Stroke is the third-leading cause of death in the United States and causes serious long-term disabilities for many worldwide.

Boerwinkle said the teams found two genetic variants on chromosome 12 near two genes that are implicated in stroke. One, called WNK1, is associated with blood pressure control and the other, NINJ2, is linked with brain injury repair.

The two genes, next to each other, both are also strongly linked with ischemic stroke, which is the most common type of stroke and is caused by blocked blood vessels in the brain.

Boerwinkle said it is not clear which specific gene is implicated, but he said the most likely suspect is NINJ2.

They found two single-letter changes in the DNA, known as single nucleotide polymorphisms or SNPs — pronounced “snips” — near NINJ2 that seem to send the strongest stroke “signal.” One is found in about 20 percent of whites they checked and 10 percent of African-Americans.

Having just one copy of this genetic variation can raise the risk of ischemic strokes by about 30 percent, he said — although the study says it is unlikely the SNPs are the actual cause of stroke but probably associated with the actual genetic cause.

The findings come from an analysis of the genetic code of more than 19,000 people in the United States and Europe taking part in four long-term studies of cardiovascular risks.

The teams were looking for SNPs among 1,544 people who had strokes, compared with 18,058 people who did not.

Boerwinkle said more work needs to be done to sort out which genes are at play, but he said the findings should give drug companies a new target for researching better treatments.

Dr. Walter Koroshetz, deputy director of the U.S. National Institute of Neurological Disorders and Stroke, which supported the study, said the findings are not strong enough to alter a patient’s stroke prevention strategy.

But he said the results “will lead scientists to direct their attention to new, important biologic mechanisms and hopefully new treatments to prevent stroke.”

Scientists uncover genetic risks for stroke

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Crestor, known chemically as rosuvastatin, reduced heart attack, stroke, need for bypass or angioplasty procedures and cardiovascular death by a surprising 45 percent over less than two years.

Results of the study, funded by AstraZeneca and called Jupiter, could help open a vast new market for statins as it shines a bright light on C-reactive protein — an indicator of arterial inflammation — and its connection to serious heart risks.

“Jupiter should dramatically change prevention guidelines,” Dr. James Willerson, director of the Texas Heart Institute in Houston, said in a statement.

“If your high sensitivity CRP (hsCRP) is high, you should be on statin therapy regardless of your cholesterol level. This is an approach we can start using tomorrow,” Willerson said.

Data from the study, presented at an American Heart Association meeting, should also help differentiate AstraZeneca’s powerful drug from rivals, such as Pfizer Inc’s Lipitor, in a crowded cholesterol market that includes generic options.

The 17,802-patient study was stopped more than two years early by independent safety monitors because the benefit from 20 milligrams of Crestor daily was so pronounced — 142 heart events with Crestor versus 251 on placebo. For every 25 patients treated, one serious heart event was avoided.

Heart attacks were cut by 54 percent, strokes by 48 percent and the need for angioplasty or bypass was cut by 46 percent compared with a placebo. Study subjects taking Crestor were also 20 percent less likely to die from any cause, a secondary goal of the trial.

EXCEEDING EXPECTATIONS

The benefits to men, women and minorities alike with healthy cholesterol levels were nearly twice what doctors expect from statins among even patients with high cholesterol.

But these were patients who under current guidelines would never be prescribed a statin — already the world’s most widely used prescription drugs — because they had excellent cholesterol levels.

“Half of all heart attacks and strokes occur in men and women with normal cholesterol,” said Dr. Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham & Women’s Hospital in Boston, who led the study.

“We’ve been searching for ways to improve detection of risk in those patients,” Ridker said.

“We can no longer assume that a patient with low cholesterol is a safe patient,” he said in an interview.

Dr. Robert Glynn, the study’s statistician, estimated that about 250,000 heart attacks, strokes, angioplasty and bypass procedures or deaths could be avoided in the United States alone if the Jupiter strategy was applied for five years.

Incidence of physician-reported diabetes was higher in the Crestor group — 245 versus 196 — a finding researchers said was consistent with other statin studies.

But incidence of cancer and cancer deaths were lower in the Crestor group — 298 and 35 for Crestor, compared with 314 and 58 on placebo.

The Jupiter data should provide a stark contrast between Crestor and rival combination cholesterol medicine Vytorin sold by Merck & Co and Schering-Plow Corp, which has been under assault from critics who say it has not proved that it cuts heart attack or death and may raise cancer risks.

Researcher have said that the cancer data from Jupiter and a controversial Vytorin study could both be a chance finding.

Volunteers in the Jupiter trial were middle-aged men and women with elevated hsCRP of greater than 2 milligrams/liter. The average was about 4 mg/liter, while the preferred level is less than 1 mg, Ridker said.

Patients on Crestor saw CRP levels drop by an average of 37 percent and LDL came down by 50 percent, researchers said.

It was not immediately clear whether the dramatic benefits were more the result of intensive LDL lowering or the impact on CRP levels.

“Getting CRP down on top of LDL lowering appears to have added incremental benefit,” Ridker said,

Reuters

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The benefit appeared stronger in those under the age of 52, according to research that was presented Sunday at the American Heart Association’s annual scientific sessions, in New Orleans.

The findings, the first to demonstrate such an effect, may help explain why the flu shot lessens the risk of cardiovascular events in people with coronary artery disease, but the real current value of the data may lie in it convincing more people to get their annual shot.

“This kind of data is super helpful to me with patients in the clinic, particularly if they’ve had a blood clot,” said Dr. Ann Bolger, the William Watt Kerr professor of clinical medicine at the University of California, San Francisco, said during a news conference on Sunday. “It’s another nail to hammer on.”

Venous thromboembolism (VTE) refers to the development of a blood clot in a vein. Such a clot can be life-threatening if breaks off and travels to the lung (pulmonary embolism).

Experts had previously known that the flu vaccine can reduce the risk of cardiovascular events in people with coronary artery disease, but it wasn’t clear why.

“We had interesting epidemiological data before that flu increased cardiovascular deaths, but we didn’t know where from,” Bolger said. “This interesting observation implies that if you get the flu shot and avoid infection, you’re less likely to get clots in the veins and arteries.”

The authors compared 727 patients with one documented episode of VTE (deep vein thrombosis or pulmonary embolism) and no history of cancer within the past five years (cancer is a risk factor for clots) with an equal number of controls with no history of clots.

Participants filled out questionnaires regarding past medical history, especially risk factors for VTE, and whether or not they had had a flu shot in the past year. They were followed for five years.

In all, 28 percent of people who had had a clot and 32 percent of controls had been vaccinated.

Individuals who had had a flu shot were 26 percent less likely to develop a blood clot.

People younger than 52 were 48 percent less likely to form a blood clot. In women under the age of 51, the risk reduction was 50 percent, and in women under 51 taking birth control pills or estrogen replacement therapy, the risk reduction was 59 percent.

Researchers can only speculate as to why the flu shot might have this protective effect.

“There is an indication that influenza can induce systemic inflammation by increasing interleukin 6,” said study author Dr. Joseph Emmerich, a professor of vascular medicine at the University Paris Descartes and head of INSERM Lab 765, which investigates thrombosis. “If it was only due to the prevention of influenza in vaccinated people, we would have a much more important decrease in the incidence [of clots] during the winter season compared to other parts of the year.”

In fact, there was no such seasonal swing.

The heart association recommends that individuals with heart disease get an annual flu shot. Patients with cardiovascular disease should get the nasal spray vaccine.

washingtonpost.com

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The researchers analyzed data from the COURAGE trial and concluded that angioplasty may add $10,000 to treatment costs “without significant gain in life years or quality-adjusted life years.”

Some of the patients received balloon angioplasty (percutaneous coronary intervention — PCI) plus optimal medical therapy, while others received optimal medical therapy alone. The study found that 4.6 years after treatment, there was no difference in the two groups’ rates of death or heart attack, but patients who received PCI did have an improved quality of life.

The researchers used Framingham study survival data to estimate patients’ life expectancy beyond the COURAGE trial. The incremental cost-effectiveness ratio (ICER) was expressed as cost per life-year and cost per quality-adjusted life-year gained.

Patient ICERs ranged from $168,000 to $300,000 per life-year of quality-adjusted life-year gained with PCI, said the researchers, who noted that there’s a reasonable probability that medical therapy alone offers better outcome at a lower cost. They found that the costs per patient for significant improvement in angina chest pain frequency, physical limitation and quality of life were $154,580, $112,876 and $124,233, respectively.

“The COURAGE trial did not find adding PCI to optimal medical therapy to be a cost-effective initial management strategy for symptomatic, chronic coronary artery disease,” the researchers concluded.

Angioplasty Not Cost-Effective for Chronic Coronary Disease – Yahoo! News

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Oh, it might cure hangovers, too, but the scientists working on it prefer to downplay that aspect of their research.

The molecule is called Alda-1, although its chemical name is “quite a bit more complicated,” said Thomas D. Hurley, a professor of biochemistry and molecular biology at Indiana University, who is working with researchers at Stanford University on the project. It has been given that name, because it activates an enzyme called aldehyde dehydrogenase 2 (ALDH2), best known until now for its role in the processing of alcohol.

ALDH2 was unexpectedly found to play a role in protecting the heart from damage, said Daria Mochly-Rosen, a professor of chemical and systems biology at Stanford, and lead author of a report in the Sept. 12 issue ofScience. In animal studies led by Mochly-Rosen, the enzyme was found to reduce the tissue damage done by unstable oxygen products called free radicals.

That finding helps explain a long-known phenomenon in which moderate drinkers tend to have less severe heart attacks than teetotalers. Alcohol, in small amounts, preconditions the heart to resist damage, but until now, the reason for the preconditioning has been unknown.

The Stanford team screened a large number of compounds to find one that would increase the activity of ALDH2. They called on Hurley for help, because “he has spent his career on this enzyme, he knows a lot about the structure of the enzyme and how it works,” Mochly-Rosen said.

Much of the research on ALDH2 has been done in Japan and China, because about 40 percent of Asians carry a variant form of the gene that makes a relatively inactive enzyme, Hurley said. “It gives rise to a number of susceptibilities, including intolerance to ethanol, beverage alcohol,” he said.

That intolerance also has medical implications. A number of studies have shown that people carrying the gene variant respond less to the nitroglycerin therapy that is a basic part of heart disease treatment, Hurley said.

And the activation of ALDH2 activity has the potential for much wider clinical applications. Free radical damage is a major feature of Alzheimer’s, Parkinson’s and other diseases, Mochly-Rosen noted.

If it fulfills its promise, Alda-1 could be given to someone in a situation where the heart is subject to free radical damage, Hurley said. It could help recovery from heart surgery, for example. The ultimate hope is that it can be given to prevent such damage.

That would require a long series of trials, and the candidate drug emerging from them might not be Alda-1, Mochly-Rosen said. With Hurley, the Stanford researchers are looking at chemical relatives that might be more effective.

Given the financial requirements of such an effort, “it would require industry to step in and do it,” Mochly-Rosen said.

And the thought of a pill that could be taken after a night on the town to make the morning after more bearable? “That is not something I would be very proud of,” Mochly-Rosen said.

“Societal issues would come from that,” Hurley said.

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"Given the potential shortcomings of Framingham-based traditional risk assessment, we wanted to know if noninvasive imaging can potentially provide incremental information," Dr. Milind Y. Desai told Reuters Health.

The study, which is published in the August issue of the American Journal of Cardiology, included 295 consecutive patients (mean age 54) with suspected cardiac symptoms, such as chest pain or dyspnea on exertion, or equivocal stress test results. Based on Framingham risk scores, 213 patients were at low 10-year risk of CHD (< 10%), 74 were at intermediate risk (10%-20%), and 8 were at high risk (> 20%).

Results of MSCT coronary angiography showed that "44% of patients in the low risk group and 75% in the intermediate risk group had evidence of proximal left anterior descending artery or left main artery plaque," Dr. Desai said. This is a concern because "most heart attacks occur in proximal lesions that are not severe."

So why do some people ostensibly at low risk have significant coronary atherosclerosis? "Current risk prediction models are old, based predominantly on Caucasian folks in Massachusetts," Dr. Desai explained. "They don’t take into account all risk factors, including obesity, metabolic syndrome, genetics, family history, and stress."

The investigators note that 51 patients below 55 years of age and 48 women were identified with proximal atherosclerotic plaque, but only 40% were on statin therapy.

Based on current guidelines, MSCT coronary angiography may be indicated in symptomatic individuals with intermediate risk scores, Dr. Desai said. "In certain low-risk individuals (e.g., those with a family history of premature CAD), I would clinically consider it," he added.

His group’s goal now is "to conclusively establish the long-term incremental prognostic value of CT angiography," the investigator said.

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