American Heart Association (AHA) 2011 Scientific Sessions
November 12-16, 2011; Orlando, FL
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Low Vitamin C Intake Associated With Elevated Marker of Inflammation and Cardiovascular Risk
Heart failure patients whose diets do not include the recommended amount of vitamin C tend to have higher levels of circulating high-sensitivity C-reactive protein (hsCRP), an inflammatory biomarker that helps predict heart disease risk, and they are more likely to die from cardiovascular causes according to a study presented at the recent AHA meeting. Conversely, lead author Eun Kyeung Song, PhD, RN, Assistant Professor, Department of Nursing, College of Medicine, University of Ulsan, Korea, said, “We found that adequate intake of vitamin C was associated with longer survival in patients with heart failure.”
The investigators recruited 212 adults discharged from an outpatient hospital after being treated for heart failure. The patients’ median age was 61 years, and two-thirds were men. Heart failure was considered severe in nearly half (45%) the patients, who had impaired left ventricular function at discharge.
Participants were asked to document everything they ate for 4 days. Information from the diaries was entered into a computer, which estimated daily vitamin C intake. The adequacy of vitamin C intake was assessed according to dietary recommendations from the Institute of Medicine (IOM), which advises men 19 years and older to obtain 90 mg of vitamin C per day from foods versus 75 mg for women age 19 years and older. Song said 82 patients (39%) in the study were found to have inadequate vitamin C intake.
Blood tests were performed to determine fasting hsCRP levels, and patients were stratified into two groups. Those at high risk for future heart disease (hsCRP level, >3 mg/L) were assigned to one group (n=98), and those at low to moderate risk (hsCRP level, ≤3 mg/L) made up the second group (n=114). After controlling for other demographic factors and clinical values, Song said individuals with low vitamin C intake were 2.4 times more likely to have an hsCRP level >3 mg/L.
Researchers followed the patients for up to 1 year, documenting time to first admission to the emergency department for a cardiovascular event or to cardiac-related death. During follow-up, 61 patients (29%) experienced a cardiac event that resulted in a visit to the emergency department, hospitalization, or death. Participants with insufficient vitamin C intake and an hsCRP level >3 mg/L were nearly twice as likely as patients with an hsCRP level ≤3 mg/L to be hospitalized for a cardiac event.
“This is the first study to demonstrate that low vitamin C intake was associated with shorter cardiac event risk survival,” said Song. She said data suggest a relationship between vitamin C deficiency and inflammatory pathways that contributes to poorer health outcomes. “An adequate level of vitamin C [intake] is associated with lower levels of hsCRP. This results in a longer cardiac event-free survival in patients,” she explained.
Terry Lennie, PhD, RN, Associate Dean of Doctoral Studies, College of Nursing, University of Kentucky, Lexington, and a study co-author, said use of diuretics in patients with heart failure might contribute to inadequate levels of vitamin C, which is a water-soluble vitamin. The study looked only at dietary sources of vitamin C, and Lennie said diet is the best way to achieve sufficient vitamin C intake. “Eating the recommended five servings of fruits and vegetables a day provides an adequate amount,” she said. Poor dentition has been linked to lower intake of vitamin C in older adults, and published data from the 2003-2004 National Health and Nutrition Examination Survey indicate that 7.2% of men and 4.1% of women aged 60 years and older have serum vitamin C deficiency.
Song recommended additional randomized controlled trials and longitudinal prospective studies be conducted to assess the impact of vitamin C and other micronutrients on survival and rehospitalization following a cardiovascular event.
—Christin Melton
The study was funded by the American Heart Association, National Institutes of Health, and National Institute of Nursing Research.
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Supervised Exercise Program Helps Patients With Peripheral Artery Disease Walk Longer
Adding a supervised exercise program to standard medical therapy for patients with claudication secondary to peripheral artery disease (PAD) allowed them to walk several minutes longer on a treadmill before experiencing pain compared with patients who received medical therapy alone or combined with stent placement; however, patients treated with stents reported greater quality of life gains. Alan T. Hirsch, MD, Director of the Vascular Medicine Program, University of Minnesota, and Chair of the CLEVER (Claudication: Exercise vs Endoluminal Revascularization) study, presented 6-month data from the multisite, randomized trial during a press briefing at the recent AHA meeting. He described PAD as a common condition that affects nearly 8 million Americans and progresses to severe walking impairment in 2 to 3 million of them. Invasive stent procedures are replacing medication and home walking as standard therapy, yet “have not been shown to offer better outcomes for patients with claudication than exercise performed in a supervised setting alone,” said Hirsch. He noted that despite evidence supporting the effectiveness of both stent procedures and supervised exercise, public and private insurers typically only reimburse stenting.
The study’s 111 patients were recruited from February 2007 to January 2010. They had moderate to severe claudication, with evidence of proximal aortoiliac disease, and were unable to walk more than 5 minutes on a treadmill. The median age of the patients was 64 years; 80% were white, and 61% were men. More than half were smokers and approximately 25% had diabetes, both major risk factors for PAD. Hirsch said ankle-brachial index scores indicated relatively severe claudication, with patients receiving an average of 68% of resting blood flow to their ankles. They had no other conditions that would limit pain-free walking and no evidence of critical ischemia.
Patients were randomly assigned to standard therapy with cilostazol, a drug that increases blood flow to the legs, and home walking; standard therapy plus stent placement; or standard therapy plus a 78-week supervised exercise program that consisted of three 1-hour sessions weekly. A nurse coordinator telephoned patients assigned to standard therapy alone to emphasize the importance of walking, risk reduction, and medication use. Overall, 71% of patients study-wide adhered to their assigned therapeutic intervention.
At 6 months, treadmill walking time was reassessed, with the supervised exercise group demonstrating an average increase in walking time of 5.8 minutes compared with average gains of 3.7 minutes in the stent group and 1.2 minutes in the standard therapy control group. Although patients in the stent group and the supervised exercise group reported better quality of life, improvement was significantly greater in the stenting group.
“It is notable that the exercise-versus-stent comparison—one of our primary outcomes—demonstrated an over 2 minute and 57% superiority of supervised exercise alone as compared to [successful] stenting,” Hirsch said, adding that both interventions bested home care. CLEVER was not adequately powered to determine why supervised exercise proved superior to stenting at increasing walking time but inferior at improving quality of life, and Hirsch said there are likely “many complex reasons” behind the contradiction. Investigators anticipate presenting 18-month findings once the study concludes in January 2012.
—Christin Melton
The CLEVER study was sponsored by the National Institute of Health’s National Heart, Lung, and Blood Institute.
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New data suggest the maximum doses of rosuvastatin or atorvastatin can treat coronary artery disease (CAD) more effectively than lower doses without compromising patient safety, reported the lead researcher for SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) at the recent AHA meeting. At a press conference, Stephen J. Nicholls, MD, PhD, Cardiovascular Director, Ohio Cleveland Clinic Coordinating Center for Clinical Research, noted that although the head-to-head comparison of these widely prescribed statins revealed only modest differences between the therapies, both treatments produced a “striking degree of regression.” In an online interview available at the event Website (http://bit.ly/q7i2Ab), Nicholls said SATURN also documented nearly 50% fewer cardiovascular events than other statin trials. “We have a very low event rate in association with [disease] regression—I think that seals the deal,” he said.
SATURN investigators recruited 1385 patients with CAD from 215 centers throughout North and South America, Europe, and Australia, and randomized them 1:1 to receive 40 mg of rosuvastatin or 80 mg of atorvastatin daily for 24 months. The majority of patients were men, and the average age was 57 years; clinical and patient characteristics were well balanced between the treatment arms. Participants underwent an intravascular ultrasound (IVUS) at the start and conclusion of the study to assess the volume of atheroma (plaque) in the walls of their coronary arteries, which was SATURN’s primary end point.
Approximately 25% of patients were lost to follow-up, leaving 1039 for the efficacy analysis. Atheroma volume declined 0.99% in the atorvastatin group versus 1.22% in the rosuvastatin group (P=.017). Although the difference was not statistically significant, “Both treatments produced marked disease regression,” said Nicholls at the press briefing. A second analysis of the IVUS images associated atorvastatin with a 4.4 mm3 reduction in total atheroma volume compared with a 6.4 mm3 reduction for rosuvastatin, which was significant (P=.01). Nicholls said the level of plaque regression, which he called “the holy grail of heart disease treatment,” far exceeded levels observed in previous clinical trials. Nearly two-thirds of participants experienced a decrease in total atheroma volume (65% in the atorvastatin group vs 71% in the rosuvastatin group). The median low-density lipoprotein cholesterol level was slightly lower in the rosuvastatin group than in the atorvastatin arm (62.6 mg/dL vs 70 mg/dL), whereas the average high-density lipoprotein level was slightly higher (50.4 mg/dL vs 48.6 mg/dL).
Despite the high-doses, no new safety concerns with either drug emerged. The atorvastatin group had a significantly greater incidence of alanine transaminase elevation, whereas the rosuvastatin group had significantly higher rates of proteinuria and creatinine kinase elevation; no cases of rhabdomyolysis were observed. Nicholls said the recent concern about a possible link between statin use and diabetes prompted investigators to check glycated hemoglobin levels, but they saw little change.
Summarizing the clinical significance of these findings in the online interview, Nicholls said, “The implications are the drugs are safe at these doses and there’s really a great benefit. We can remove the plaque, and we know that will translate to a reduction in clinical events.” Data from the SATURN study were simultaneously published in the New England Journal of Medicine.
—Christin Melton
This study was funded by AstraZeneca.