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The AmericanCollege of Cardiology’s (ACC) Annual Scientific Session is the largestyearly cardiovascular meeting, bringing together cardiologists & cardiovascular specialists around the world to share the newest discoveries in treatment & prevention, while helping the ACC achieve its mission to address & improve issues in cardiovascular medicine.ACC.08 was the 57th meeting & was held in Chicago, USA, between March 29 & April 1, 2008. Rapid weight gain in the first weeks of life may boost heart disease risk Appropriate medical attention & Nutrition Needed to Protect Infants Low birth weight, especially in premature babies, has been associated with poor heart health in adulthood, resulting in the traditional view that rapid weight growth after birth may be protective. However, new evidence suggests that accelerated growth in preterm & term babies is associated with a range of diseases in later life, such as heart attack, diabetes & high blood pressure, according to a study presented on March 29, 2008 at theAmerican College of Cardiology’s 57th Annual Scientific Session. Researchers found that rapid weight gain during the first two months of life is linked to 0.5mmHg increase in systolic blood pressure and increased arterial stiffness (a marker of damage to the arteries) at as early as 10 years of age. “It appears there is a window early in life where programming for later cardiovascular disease can occur, and nutrition may play a significant role,” said Marietta Charakida, M.D., Ph.D., of University College London, and lead study investigator. “This study shows that targeting cardiovascular prevention in adulthood or even childhood may not be enough and nutritional strategies implemented early in life might offer additional benefit.” “Accelerated weight gain in first few weeks of life might have a detrimental effect on cardiovascular health. Thus, medical attention, and appropriate nutrition early in life might be necessary to reduce this risk,” adds Dr. Charakida. Morbid Obesity Levels the Playing Field When It Comes to Gender-Related Cardiovascular Risk Excess Obesity May Be Somewhat Protective for Ischemic Heart Disease Heart disease remains the leading killer of men & women; but while men tend to be at greater risk for developing heart problems, cardiovascular risk profiles often vary between genders. A new study suggests such gender-related differences disappear in patients who are morbidly obese compared to those who are overweight or obese, according to data presented on March 29 at ACC.08.Researchers attribute this phenomenon to high levels of estrogen in men with morbid obesity, which makes them more similar to females than their overweight of obese counterparts. “Our data suggests that patients’ cardiovascular risk profile is associated with their gender largely because of differences in hormones. When these differences are reduced, as we see in morbidly obese patients, risk factors are similar,” said Luigi Biasucci, M.D., of CatholicUniversity in Rome. “These findings suggest that the relationship between risk factors and disease may be more complex than believed.” Morbidly obese patients have high levels of estrogen due to expanded subcutaneous fat tissue (stored under the skin), which converts the male sex hormone, androgen, into estrogen through a converting enzyme, called aromathasis. Excess obesity does not carry additional cardiovascular risk, according to the data. In fact, morbidly obese subjects appear to have a lower incidence of high blood pressure and cholesterol—both important risk factors for heart disease. “Morbid obesity may be somehow protective due, in part, to increased estrogen levels,” said Dr. Biasucci. “The risk of ischemic heart disease and heart attack is lower in morbidly obese patients compared to those who are overweight or obese. However, these patients may have a higher risk of heart failure, cancer and pulmonary disease, so it’s certainly not safe.” Researchers believe cardiovascular risk needs to be differentially assessed in patients with morbid obesity compared to others. This will better inform patients’ treatment plan. “For morbidly obese patients, it may be less important to focus on triglycerides and cholesterol than to encourage weight loss,” adds Dr. Biasucci. “This doesn't mean these patients can drink [alcohol] excessively, smoke, not reduce high cholesterol and so on, but differentiating their risk profile can help clinicians prioritize efforts to reduce cardiovascular risk.” The Anniversary of a Loved One’s Death Can Trigger Sudden Death Anniversary Effect Linked to Unexpected Cardiac Deaths If the date of a loved one’s passing is approaching, beware. The anniversary of the death of a close family member, especially a mother or father, is a significant trigger for Sudden Death (SD), especially in men, according to research presented on March 29 at ACC.08. Understanding the triggers of SD --- death that is unexpected & occurs rapidly, frequently within one hour of the onset of symptoms & usually due to lethal arrhythmias --- may help researchers discover ways to anticipate & prevent premature loss of life.Sudden death is a major public health problem & is responsible for nearly half of all cardiac deaths. “We’ve all known close family members who have died within hours, weeks, months or years of each other. The anniversary of death appears to be a devastating trigger of sudden death,” said Ivan Mendoza M.D., Central University of Venezuela, and investigator of the study. “Physicians should be aware that mental stress, such as the anniversary effect, may induce sudden death in susceptible individuals.” According to Dr. Mendoza. patients may be especially vulnerable if they have a history of heart attack, family history of sudden death or coronary disease, and cardiovascular risk factors such as high cholesterol, high blood pressure, diabetes, smoking, obesity or a sedentary lifestyle. Psychological factors associated with coronary artery disease like anger, stress, emotional trauma, depression or anxiety are also linked to sudden death. Nearly 80 percent of the patients (n=10) who died suddenly under the anniversary effect were male. The reason for this is not understood, but may reflect gender differences in response to stressful situations. Dr. Marques, co-investigator of the study,says that women could be less susceptible to higher levels of stress hormones including catecholamines due to protective mechanisms from certain molecules, including estrogens and protein Gi response pathways, which are thought to prevent damage to the heart. This and previous studies have indicated that cardiovascular mortality is affected by the anticipation or experience of psychological factors and symbolic occasions. These findings may have implications for clinical practice and for research, according to the researchers. “Avoidance of stress is not possible for individuals leading a full life,” said Dr. Mendoza. “However, integrative medicine, including psychological management, stress reduction interventions, and the development of tailored behavioral interventions based on individual patient risk factors, may be warranted.” Smoking Is Greatest Predictor of Recurrent Cardiac Events Among Young Heart Attack Survivors Researchers Emphasize Importance of Smoking Cessation for Long-Term Hear Health Continue to smoke following a heart attack is the most powerful predictor for recurrent cardiac events among survivors age 35 years or younger. (March 29, ACC.08) In particular, patients who continue to smoke have approximately 3 times the risk for future heart problems (e.g. cardiac death, a repeat heart attack or revascularization due to clinical deterioration) compared to those who quit smoking after the first acute myocardial infarction (AMI) or heart attack. This higher risk is independent of the type of treatment, presence of other cardiovascular risk factors (e.g. high cholesterol, high blood pressure, diabetes mellitus or body mass index) and even the function of the left ventricle (ejection fraction), which is a well-established, strong predictor of future cardiac events. “This study suggests that smoking plays a major role not only in the development of AMI, but also in future coronary events,” said Loukianos Rallidis, M.D., of the University General Hospital Attikon in Greece, and lead study investigator. “Patients who have suffered a heart attack very early in life can significantly improve their long-term prognosis by quitting smoking and adopting a healthier lifestyle, in addition to following the treatment plan set forth by their cardiologist.” “It is imperative for the health system to provide effective smoking cessation programs as part of the holistic treatment of coronary heart disease,” said Dr. Rallidis. “Smoking is a modifiable risk factor and its effect is largely reversible.” According to Dr. Rallidis there has been a progressive increase in the number of young people suffering AMI, which is partially due to unhealthy dietary habits, lack of routine physical exercise and a high proportion of smoking among young people. A previous study by Dr. Rallidis’s group found that the majority of patients (95 percent) experiencing a heart attack before the age of 36 years were smokers. This translated to a 6-fold increased risk of AMI before 36 years of age compared to non-smokers - regardless of the presence of high cholesterol, high blood pressure or diabetes mellitus. Patients with Heart Failure Vulnerable to The Flu, Despite Annual Vaccination Influenza Contributes to Increased Hospitalizations & Deaths in these Patients Coming down with influenza, or the flu, can be potentially life-threatening for patients with heart failure (HF) and other heart conditions, which is why annual influenza vaccination is widely recommended. However, these patients may not be adequately protected, despite widespread immunization. New research finds that individuals with heart failure have lower immune responses to the vaccine compared to healthy individuals of similar age, placing them at even greater risk for influenza-related hospitalization or death. (ACC.08) “Patients with heart failure are unable to mount as vigorous an immune response, which leaves them more vulnerable to infection,” says Orly Vardeny, Pharm. D. of the University of Wisconsin School of Pharmacy & lead investigator of this study. “Better strategies need to be devised to minimize infection-related complications & death, & lower health care cost.” He also stressed that these data should not preclude HF patients from annual vaccination; however, other preventive steps might be needed to bolster protection from the virus. The reason why HF patients have reduced immune responses is unknown, but researchers are exploring this question. Influenza causes 36,000 deaths & more than 200,000 hospitalizations in the U.S. each year. Lowering or Keeping Anxiety Levels in Check Dramatically Reduces Heart Attack or Death in Patients with Heart Disease Those who can calm down can also liver longer, healthier lives Anxiety is a normal reaction to life’s stressors; however, if left unchecked, such angst can spell trouble for patients with coronary artery disease --- a leading type of heart disease. By taking steps to lower anxiety levels over, time, these patients can significantly decrease their risk of heart attack & even death. (ACC.08) “Psychological stress, be it depression or anxiety, has been linked to the progression of atherosclerosis, development of atherothrombosis and increased risk of arrhythmias,” said Yinong Young-Xu, Ph.D., of the Lown Cardiovascular Research Foundation, and lead investigator of this study. “Very few studies, however, have tried to examine whether we can improve cardiovascular outcomes if we assess patients’ mental health and work to reduce levels of depression or anxiety through the use of medications, good patient-doctor relationships and/or psychotherapy.” This is the first observational study to examine the impact of treating anxiety on cardiovascular outcomes, according to Dr. Young-Xu. Results indicate that patients who reduced or kept their anxiety level steady were up to 60% less likely to have a heart attack or die compared to those who had an increase in anxiety level. This association remained after adjusting for other potential cardiovascular risk factors. The researchers stressed the importance for physicians to attend to the whole patient by paying attention to psychological problems in addition to cardiovascular disease, adding that the lifetime prevalence of anxiety disorder is around 30% among heart disease patients. School-Aged children’s Intellectual Potential Hindered by Congenital Vascular Abnormalities Surgery May Restore School Performance School-aged children with untreated vascular ring (VR) abnormalities --- malformations in the main vessels coming out of the heart that often develop before birth --- have lower intellectual capabilities than healthy children. These effects are reversible after surgery, the standard treatment for VR. (ACC.08) “Our study suggests early diagnosis and treatment of these abnormalities are needed to preserve and promote intellectual performance in school,” said Shuping Ge, M.D., of the Baylor College of Medicine and Texas Children's Hospital, Houston, Texas. “After undergoing surgical intervention, children with VR showed dramatic improvements in intellectual performance across a variety of tasks.” Currently, the indication for surgery for congenital VR abnormalities is based on symptoms of tracheal and esophageal compression early in life, but not all children exhibit these symptoms. “Children with subtle symptoms of breathing or swallowing difficulties, or recurrent respiratory infections, may still be indicated for surgical intervention to restore their intellectual performance if our findings are further validated,” said Dr. Ge. “In this regard, our study raised an important question and challenged the traditional paradigm of relieving VR only when it is clinically significant.” “Our study suggests early diagnosis and treatment of these abnormalities are needed to preserve and promote intellectual performance in school,” said Shuping Ge, M.D., of the Baylor College of Medicine and Texas Children's Hospital, Houston, Texas. “After undergoing surgical intervention, children with VR showed dramatic improvements in intellectual performance across a variety of tasks.” Currently, the indication for surgery for congenital VR abnormalities is based on symptoms of tracheal and esophageal compression early in life, but not all children exhibit these symptoms. “Children with subtle symptoms of breathing or swallowing difficulties, or recurrent respiratory infections, may still be indicated for surgical intervention to restore their intellectual performance if our findings are further validated,” said Dr. Ge. “In this regard, our study raised an important question and challenged the traditional paradigm of relieving VR only when it is clinically significant.” Tissue Doppler Imaging Surpasses Conventional Echocardiography in Predicting Mortality Adults over the age of 40 have a 20 percent lifetime risk of developing heart failure, a condition with high morbidity and mortality. Echocardiography, together with a history and physical examination, has been an essential part of the evaluation of patients with suspected heart failure; however, echo reveals evidence of heart failure in only half of affected individuals. Now, a newer echocardiographic method called Tissue Doppler Imaging (TDI) appears to be better at diagnosing heart failure and predicting adverse outcomes, including death, according to a study presented on March 31 at ACC.08 “TDI identified persons with high risk of dying during the follow-up period and it was definitely superior to conventional echocardiography. Our results may pave the way for the introduction of TDI into standard clinical echocardiographic examination. The information it gives could allow patients to take measures proactively to prevent or delay their death from heart disease,” said Rasmus Mogelvanc, M.D., of GentofteHospital, Copenhagen University, Denmark, & lead author of the study. Novel Imaging Technique Reveals Benefit (or Not) of Lipid-Lowering Therapy Aggressive atorvastatin treatment guided by USPIO-enhanced MRI reduced inflammation & stroke risk in selected patients Treatment options for people with diseased coronary or carotid arteries have traditionally been based on the degree of stenosis, or narrowing, of the vessel. More and more, however, studies reveal that stenosis is just one piece of the atherosclerosis puzzle and that other factors, including inflammation, also play a role. A novel technique that uses a unique contrast agent during high-resolution magnetic resonance imaging can detect macrophage activity – a sign of inflammation – and is allowing clinicians to individualize their treatment for atherosclerosis and improve outcomes. (ACC.08) In the study, patients with carotid artery disease were imaged with USPIO (Ultra Small Particles of Iron Oxide)-enhanced high-resolution MRI to determine their inflammation levels. Study participants were then randomized to receive either 80 mg (aggressive high-dose therapy, n=20) or 10 mg (low dose, n=20) atorvastatin daily for 12 weeks. Both groups were imaged at 6 and 12 weeks to document any changes in the degree of inflammation as well as the number of small clots, or emboli, given off by the plaque in the diseased artery. By 12 weeks, both inflammation and emboli were significantly reduced in the aggressive, high-dose group compared with the low-dose group. “The real star of this study is this new way of imaging, which allows you to zero in on what is actually going on in these arteries. Once you know this, then you can individualize therapy accordingly,” said Jonathan H. Gillard, M.D., Academic Neuroradiologist, CambridgeUniversity, Cambridge, UK, and study coauthor. “This study tells us that if you randomize patients who have inflammation of the carotid artery to a high dose of atorvastatin, you substantially reduce the amount of inflammation and risk of stroke, whereas low dose atorvastatin does not reduce risk. And thanks to this imaging technique, we can now figure out which patients need the aggressive treatment before we begin our therapy. This novel MRI can allow us to give better targeted care to the individual patient; this is personalized medicine.” Rosuvastatin Regresses Coronary Atherosclerosis by Quantitative Coronary Angiography Results of a study known as ASTEROID (AStudy to Evaluated the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden), designed to determine the effects of treatment with rosuvastatin on progression of coronary atherosclerosis in patients who had a clinically indicated cardiac catheterization that showed angiographic evidence of coronary artery disease (CAD), were presented at the ACC.08 The ASTEROID trial showed that rosuvastatin treatment for 24 months to average LDL-C (low density lipoprotein cholesterol, the “bad” cholesterol) levels well below 70 mg/dL, accompanied by significant increases in HDL-C (high-density lipoprotein cholesterol, the “good” cholesterol), produced regression by decreasing percent diameter stenosis & improving minimum lumen diameter (MLD) as measured by QCA (quantitative coronary angiography) in coronary disease patients. Previous studies using QCAdemonstrated that statin therapy slows progression of coronary stenoses in proportion to average LDL-C levels during therapy. However, no statin monotherapy study has achieved either halting of progression or regression of angiographic disease. ASTEROID assessed whether rosuvastatin could regress coronary atherosclerosis by intravascular ultrasound (IVUS, the primary endpoint) and QCA (a secondary endpoint). ASTEROID was a prospective, multicenter, international open-label trial that enrolled men and women 18 years or older with a clinical indication for coronary catheterization and angiographic evidence of CAD who met specific angiographic and IVUS criteria. Results indicated that rosuvastatin:
“ASTEROID’s two imaging modalities, which clearly measured different parameters and focused on different segments of the coronary arteries, demonstrated concordant improvements in angiographic measurements of lumen dimension and IVUS measurements of atheroma volume consistent with regression and stabilization of atherosclerosis with intensive statin therapy,”said Dr. Christie M. Ballantyne, M.D., Section of Atherosclerosis & Vascular Medicine, Department of Medicine, Baylor Coolege of Medicine, & the Methodist DeBakey Heart & Vascular Center & lead author of the study. Avoiding Cardiovascular Events Through COMbination Therapy in Patients LIving with Systolic Hypertension, the Early Termination of the ACCOMPLISH Trial for Efficacy ACCOMPLISH (Avoiding Cardiovascular Events Through COMbination Therapy in Patients LIving with Systolic Hypertension) is the first trial to evaluate cardiovascular outcomes using single pill, fixed-dose combination therapy for the treatment of high-risk hypertensive patients. The trial was terminated early & the interim results presented at ACC.08 Patients with hypertension & high risk for cardiovascular complications experienced 20% fewer events (cardiovascular death, heart attacks, strokes, hospitalizations for unstable angina & need for coronary heart procedures) when treated with a combination of an ace inhibitor & calcium channel blocker (ace/ccb) compared to a combination of an ace inhibitor & hydrochlorothiazide (ace/hctz). The ACCOMPLISH investigators demonstrated that the ace/ccb tablet not only reduced death from heart attacks but also retarded the progression of heart disease by reducing the number of heart attacks, hospitalizations for unstable heart blockages, and even the need for procedures to open clogged arteries to the heart. The strategies used in ACCOMPLISH differ from the current guidelines most clinicians follow. Current guidelines recommend initial treatment with tablets that contain one drug. Importantly, present guidelines recommend diuretics as initial therapy for most hypertensive subjects. Most people with hypertension do not have adequate control of their blood pressure. Similarly, only 37 percent of the participants in the ACCOMPLISH trial had adequate control prior to entry into the trial. The use of combination tablets as the initial drug treatment more than doubled the number of patients that achieved adequate control. Moreover, the use of ace/ccb combination tablet provided superior cardiovascular protection when compared to the diuretic-based therapy. “The ACCOMPLISH trial demonstrates the superiority of an ace/ccb pill fixed-dose combination treatment strategy for reducing cardiovascular morbidity and mortality and provides evidence to modify future hypertension guidelines,” said lead investigator of the ACCOMPLISH study Kenneth Jamerson, M.D., Professor, University of Michigan. Dr. Jamerson added, “ACCOMPLISH was both an innovation in hypertension trial design (initial combination rather than monotherapy) and challenged a standard of care in the management of hypertension (diuretic based therapy).” The Novartis-funded ACCOMPLISH trial achieved exceptional blood pressure control and reduced cardiovascular morbidly and mortality by 20 percent with the use of a combination tablet containing an ace inhibitor/calcium channel blocker. The results provide important new health benefits for the millions at risk of complications from hypertension. Cardiovascular Risk Differs by Celecoxib Dose New Findings May Help Guide Treatment Decisions for Patients who Benefit from Selective Cox-2 Inhibition Research presented at ACC.08 suggests tha physicians should prescribe the lowest doses of celecoxib possible, especially in higher risk patients. Results of this trial showed evidence of dose & regimen differences in risk, as well as evidence of an interaction between baseline cardiovascular risk & celecoxib dose, and suggest that the adverse effect of dose is most pronounced in higher risk patients. “Data from this study should provide some measure of comfort in prescribing Celecoxib to patients with very low cardiovascular risk,” said ScottD.Solomon, Director, Noninvasive Cardiology, Brigham & Women’s Hospital, & lead investigaor of the study. “Similarly, we should be cautious in prescribing celecoxib to patients who have elevated baseline cardiovascular risk. The datasupport the recent American Heart Association scientific position statement suggesting that physicians should prescribe the lowest doses of Celecoxib possible, especially in higher risk patients.” Specific Blood Glucose Lowering Strategy Prevented the Progression of Coronary Atherosclerosis in Diabetic Patients New Study Demonstrates Relationship for First Time Heart disease is the leading cause of death in diabetics, responsible for more than 75 percent of mortality in these patients. While management of blood glucose levels (glycemic control) is one of the principal treatment goals of diabetes therapy, it has been difficult to demonstrate a favorable effect of glycemic control on arterial complications, such as buildup of plaque. Previously, no diabetes therapy regimen has shown the ability to reduce the progression of coronary atherosclerosis, or build-up of plaque, within the arterial walls. For that reason, there has been little evidence to support a preference for one class of anti-diabetic medication over another as a means to reduce atherosclerotic disease. According to the PERISCOPE trial (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation), presented at ACC.08, one of two approaches to diabetes management proved more effective at slowing the progression of atherosclerosis in patients with type 2 diabetes, the most common form of diabetes in adults. PERISCOPE compared the effects of two widely used yet distinctively different classes of oral glucose-lowering agents on the rate of progression of coronary atherosclerosis in diabetic patients, measured using intravascular ultrasound. Patients were randomly assigned to receive a thiazolidinediones (TZD), pioglitazone, a relatively new type of drug that reduces blood glucose by increasing insulin sensitivity or a sulfonylureas, glimepiride, that lowers blood glucose by acting as an insulin secretagogue (stimulates insulin release by the pancreas). The principal finding was an absence of progression of coronary plaque buildup with pioglitazone (-0.16%) compared with highly significant progression with glimepiride (+0.73%). “Atherosclerosis can be particularly aggressive in patients with diabetes, which is currently increasing at an alarming rate in the developed and developing world,” said Steven Nissen, M.D., Chairman, Department of Cardiovascular Medicine, Cleveland Clinic and lead author. “By defining the optimal strategy for managing coronary heart disease in this patient population, this study has major implications for how we will treat diabetics with coronary disease in the future.” New Study Shows That Experimental Weight Loss Drug May Slow the Progression of Heart Disease While studies have shown a correlation between abdominal obesity and heart disease, no clinical trials have demonstrated a benefit for weight management drugs in coronary disease patients. The Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant - The Intravascular Ultrasound Study (STRADAVARIUS), presented today at ACC.08, suggests that treatment with rimonabant may slow the progression of coronary disease in abdominally obese patients. Rimonabant is an experimental agent not yet approved in the United States, but is available in some European countries. This drug represents the first of a new class of drugs that work by inhibiting cannabanoid type 1 (CB1) receptors. These receptors are stimulated when people smoke marijuana, causing a ravenous appetite commonly known as the “munchies.” Blocking CB1 receptors result in reduced food intake, an increase in HDL (“good”) cholesterol, and reductions in triglycerides and C-reactive protein (CRP). Patients experience sustained decreases in body weight and reductions in waist circumference. Since atherosclerosis progression is accelerated by risk factors such as elevated LDL (“bad”) cholesterol and triglycerides, lower levels of HDL, high systolic blood pressure and diabetes, investigators sought to examine if rimonabant could slow the progression of coronary atherosclerosis in abdominally obese patients with the metabolic syndrome and preexisting coronary disease. The STRADIVARIUS Trial randomized 839 patients at 112 centers in North America, Europe and Australia to receive either rimonabant or placebo and measured progression of disease by intravascular ultrasound, a technique that directly measures plaque buildup in the coronary arteries. Patients treated with rimonabant lost about 9.5 pounds and 1.8 inches in waist circumference. HDL cholesterol rose 22.4 percent, triglycerides decreased 20 percent and CRP levels decreased 50 percent. The primary endpoint, a calculation of disease burden known as Percent Atheroma Volume, did not show a statistically significant effect, but the secondary endpoint, the Total Atheroma Volume did show a statistically significant effect, p 0.03. The success or failure of a clinical trial is judged by the primary endpoint. Therefore, the study failed to meet its principal objective. However, the positive results for the secondary endpoint suggest that this approach has the potential to reduce plaque buildup in the coronaries, which will need to be confirmed in further trials.
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