It seems as if almost every week a groundbreaking study is released with implications on the management, prevention or treatment of cardiovascular disease. From rapid discoveries tied to our ever-increasing understanding of the human genome to evidence-based reconfirmation of what many physicians are already putting into practice, each of these reports adds to our body of knowledge as we seek to understand America's number one killer.
As part of its year-end report, the American Heart Association creates an annual "top 10" list highlighting some of the most significant research advances during the past calendar year. The recently released 2005 list covers a broad spectrum from a smoking cessation drug to cell recycling to MI risk from prehypertension.
Dr. Robert Eckel, president of the American Heart Association, says, "The importance of the top 10 is that it covers a breadth of topics. It's a nice mix of basic science and clinical medicine."
He adds, "We're looking at evolving technology such as ICDs and genotypes, very practical public health concerns such as smoking, and epidemics that are worldwide like childhood obesity."
1. Cell recycling to improve heart function: Topping the 2005 list is the use of a patient's own cells to mitigate damage. In two separate German studies, heart function was improved and the effects of peripheral vascular disease lessened by infusing stem-like cells into the patient.
Reporting on the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) – a randomized, double-blind, placebo controlled multicenter trial – researchers showed patients who received the infusion treatment had nearly twice the improvement in their hearts' pumping function compared to those given a placebo.
In the trial, 204 patients were randomized to receive either intracoronary infusion of bone marrow progenitor cells (BMC) or placebo three to six days after their infarction. All were brought in for left ventriculography at four months. The baseline characteristics between the 103 who received a placebo and the 101 who received BMC were very similar. At the follow-up, the BMC group had nearly twice the ejection fraction improvement. For those with greater degrees of left ventricular dilation (an EF<49 percent), the improvement was almost three times that of the placebo group.
The second trial showed that implanting BMC into the blood-starved legs of patients suffering from peripheral arterial disease improved their overall ability to walk longer and their quality of life.
"The ability to improve myocardial function and limit infarct size is an important therapeutic advance and offers much promise," says Dr. Eckel. "We're not ready to employ this technology at a small, rural hospital, but I think we're ready to validate these studies and maybe move to a broader application."
For more information, see www.americanheart.org/presenter.jhtml?identifier=3035453.
2. Varenicline for smoking cessation: Also from European clinical trials, the drug Varenicline was found to stimulate the brain receptors that channel the habit-forming properties of nicotine. During the 12-week studies and 40-week observational follow-up, nearly 2,000 patients received either Varenicline, bupropion or placebo. Quit rates were confirmed during weeks nine through 52 by measuring carbon monoxide in a participant's expired breath.
Quit rates for those who received Varenicline equaled about 44 percent compared to 30 percent in the bupropion group and only 17.7 percent in the placebo group.
"Smoking remains a major concern for increased risk factors for cardiovascular disease and cancer," says Eckel. "Anything we can do to facilitate smoking cessation has got to be an upbeat message."
For more information, see www.americanheart.org/presenter.jhtml?identifier=3035500.
3. Scientific statement on the consequences of childhood obesity and suggested prevention strategies to combat the problem: While quick to point out the AHA is also interested in combating adult obesity, Eckel says the preventative emphasis is on children. The scientific statement "Overweight in Children and Adolescents: Pathophysiology, Consequences, Prevention and Treatment" outlines the latest data on the epidemic and offers ideas for prevention strategies.
About 16 percent of today's children and adolescents are classified as overweight, but this is a figure that has almost quadrupled in the past 40 years.
As with other interested groups, the AHA is calling for a multidisciplinary prevention approach involving parents, schools, government, the entertainment and food industries and healthcare providers.
The AHA is calling on physicians to plot BMI annually along with height and weight. Children with a BMI between the 85th and 95th percentiles should be considered "at risk" of overweight.
While Eckel points out that height is certainly a variable between the ages of nine and 18, he says, "The idea is bringing attention to the physician, parents of the child, and the child themselves, if they are old enough to understand, and begin modifying weight gain."
Above the 95th percentile, Eckel says a more active intervention is required.
For more information, see www.americanheart.org/presenter.jhtml?identifier=3034808
4. RAVEL results underscore benefits of drug-eluting stents: At the three-year follow-up, the rate of major adverse cardiac event for those treated with drug-eluting stents was half that of patients who received metal stents. For those treated with CYPHER stents, the MACE rate was 15.8 percent compared to 33.1 percent for the metal stent control group. The study focused on the CYPHER stent, which is coated with sirolimus, and outlined survival rates without additional reopening procedures and without vessel failure.
Survival rates without a second revascularization at the one-year mark were 99.2 for the sirolimus group and 75.9 for the bare metal control. At the three-year mark, the rate was 93.7 for sirolimus and 75 for bare metal. As for survival rates without vessel failure, it was 95.8 at the one-year point for sirolimus vs. 71.2 for bare metal. At three years, the rate was 87.9 for sirolimus and 67.3 for bare metal.
"I think this is the period after the sentence confirming what was probably already known," says Eckel.
For more information, see Circulation: 2005; 111:1040-1044.
5. Spotlight on ethnic and racial disparities in CVD care: This past March, the AHA held a press conference in New York to highlight the racial and ethnic disparities featured in that month's issue of Circulation. Disparities and barriers to care ranged from a lack of cultural sensitivity within the healthcare delivery system to inadequate minority participation in clinical trials to clear differences in treatments offered.
One example cited was from a report by the Kaiser Family Foundation/American College of Cardiology Foundation that showed physicians used thrombolytic therapy 50 percent less often with African-Americans than with white patients.
However, Eckel cautions that it is important to look at the big picture to see if there are underlying medical reasons for the disparity.
"The African-American population is more likely to be hypertensive," he points out. "Therefore, the risk of a cerebral bleed is higher."
He continues, "Nevertheless, I think many disparities are not adequately based. One would hope that only evidence-based decisions are made, but bear in mind a lot of decisions in medicine are made without that evidence available."
To begin to effect change in our care system, Eckel suggests a three-pronged approach. "Disparities need to be identified, their source clarified and steps taken to ameliorate the disparity," he says.
For more information, see Circulation: 2005; 111; 1332-1336.
6. Effects of secondhand smoke almost as harmful as smoking: A meta analysis of 29 studies shows an accumulation of compelling evidence that secondhand smoke … or passive smoking … has a much larger impact on the cardiovascular system than might be expected. Passive smokers have a 30 percent risk increase for coronary artery disease. The impact of secondhand smoke is similar to, but even larger than, the effects of air pollution.
"As we increasingly see evidence that secondhand smoking is dangerous, we can look at the political process to impact that favorably," says Eckel of the importance of this evidence-based approach. "The idea of banning smoking in public places is justified by this research."
For more information, see Circulation: 2005; 111; 2684-2698.
7. Extending the range of patients who could benefit from an ICD: First presented at the American College of Cardiology meeting in 2004 and reported in the New England Journal of Medicine in 2005, this study of 2,521 patients randomized treatment for heart failure patients to see the impact of implantable defibrillators. Patients with class II or III heart failure and a left ventricular fraction of 35 or less received one of three therapies: conventional heart failure therapy plus a shock-only, single-lead ICD; conventional therapy plus amiodarone; or conventional therapy plus placebo. The causes of congestive heart failure among the total population were 52 percent ischemic and 48 percent non-ischemic. At the median follow-up of just under four years, there was a 29 percent death rate in the placebo group, a 28 percent death rate in the amiodarone group and a 22 percent death rate in the ICD group. The conclusion was that while amiodarone therapy had no real impact on survival rates, using the ICD therapy effectively had a 23 percent decrease in mortality.
"This study extended who benefits from ICDs to people with non-ischemic cardiomyopathy class II or III heart failure with a wide variety of myocardial pathology," Eckel says in regard to the significance.
For more information, see the New England Journal of Medicine; http://content.nejm.org/cgi/content/short/352/3/225.
8. Effects of thermal stimulation on stroke victims: Researchers found that alternating heat and cold could help rehabilitate a stroke victim's paralyzed upper limbs. After just a few weeks of therapy, participants had a significant enhancement in sensory and motor function in their arms and hands. In the small study of 46 survivors of acute stroke, patients received either conventional therapy alone or conventional therapy plus thermal stimulation for 20 to 30 minutes a day, five days of the week for six weeks.
"Trying to improve stroke outcomes is something the American Heart Association and American Stroke Association is very focused on," says Eckel. "This demands additional study, but of the six criteria assessed, over half of those outcome variables improved with thermal therapy compared to standard therapy."
For more information, see Stroke: Dec. 2005; 36: 2665-2669.
9. ADRB2 genotype may predict MI survival rates: Researchers discovered that survival rates from beta-blocker treatment were favorably impacted if patients had a genotype known as ADRB2. Studying 735 acute coronary artery syndrome patients in Kansas, researchers found the ADRB2 patients who had been given beta-blockers had almost twice the survival advantage.
Eckel was quick to point out that beta-blocker is still the standard therapy and that giving beta- blockers to those who did not have the genotype ADRB2 did not harm them; the beta-blockers just didn't help them like they helped those in which the genotype was present.
"We're at the early phase of pharmacogenomics," Eckel says. "In the next decade, there may be a rapid turnaround test (for ADRB2), but we're not there yet."
Eckel adds, "Physicians should stay interested and stay informed, but it's not yet ready for prime time."
For more information, see JAMA: 2005; 294; 1526-1533
10: Prehypertension triples the risk of heart attack: By examining existing data from the landmark Framingham Study, researchers found a prehypertensive person is more than three times as likely to have a heart attack and almost twice as likely to have heart disease than a person with normal blood pressure.
Prehypertension, the gray area between normal blood pressure and hypertension, is defined as a systolic pressure between 120 and 139 and/or a diastolic pressure between 80 and 89 mm Hg.
"I think that now that we understand the relevance of prehypertension, more studies need to be carried out to show the benefit or lack thereof of early intervention," says Eckel. "It sets the stage to show whether or not early intervention is warranted."
