A study led by Richard Scheffler, Berkeley Professor of Health Economics and Public Policy, found that low-income individuals who had previously suffered heart problems are less likely to be affected again if they live in a county with higher measures of trust, cooperation and social networks. This situation is known as ‘social capital’. These findings held true even when other variables, such as gender and age, were taken into consideration.
“This analysis points to a real effect on real people,” said Scheffler. “It speaks to the value of clubs and social organizations in providing health information and reducing stress, both of which are known to reduce heart disease.”
The investigators measured the degree of social capital in any given county based on the number of people employed in various organizations, including religious, civic, political, social and alumni groups.
The investigators used a retrospective cohort study design of 34,752 individuals aged 30–85 years, who were hospitalized for acute coronary syndrome in Northern California between 1998 and 2002. Patients were tracked for symptoms of recurring heart problems.
“An area with a high density of social networks and resources changes the character of a community, regardless of whether any one particular individual joins or not,” said Scheffler. “It’s the opposite of having a liquor store on every corner. You don’t have to shop at the liquor stores to be impacted by the type of environment they create.”
“This is the first study to demonstrate a link between community social capital and prognosis following heart disease,” said study coauthor Ichiro Kawachi, Professor of Social Epidemiology in the Department of Society, Development and Human Health at the Harvard School of Public Health (MA, USA).
“Other research has linked social capital to health outcomes, but most of these studies have been cross-sectional, and therefore difficult to draw conclusions about cause-and-effect relationships. The findings of this study take us in the right direction.”
“The majority of information available about the determinants of health is based upon individual behavior,” said Leonard Syme, Berkeley Professor Emeritus of Epidemiology and study coauthor. “This study clearly shows that the world within which people live also has an important impact on health.”
Source: Scheffler RM, Brown TT, Syme L, Kawachi I, Tolstykh I, Iribarren C. Community-level social capital and recurrence of acute coronary syndrome. Soc. Sci. Med. 66(7), 1603–1613 (2008); www.berkeley.edu
New pathway found in β-blockers for heart failure
To date it has been thought that β-blockers, which are used in the treatment of millions of heart failure patients worldwide, work by acting directly on the heart. However, a recent study conducted at University College London (UK), has discovered that this may not be the only pathway and the drugs may also act via the brain. In the future, therapies for cardiovascular diseases could target the CNS.
Based on a rat model, the study has found that metoprolol, which is a β-adrenoceptor blocker, slows the progression of heart failure by acting directly on the brain. It appears that the β-blocker acts on a localized group of brain cells, which was previously identified by the same group of researchers as playing a key role in the control of both blood pressure and heart rate.
Coauthor Alexander Gourine, concludes, “Many people have assumed that β-blockers have a direct salutary influence on the heart, but our findings challenge this view, suggesting that β-blockers may act directly in the brain and this action could underlie their beneficial effect on the failing heart. This study suggests that novel ways might be found to treat cardiovascular disease aimed at sites within the brain.”
Source: Gourine A, Bondar SI, Spyer KM, Gourine AV. Beneficial effect of the central nervous system β-adrenoceptor blockade on the failing heart. Circ. Res. DOI: 10.1161/CIRCRESAHA.107.165183 (2008).
Genotype that predicts initial warfarin response identified
The importance of obtaining the correct dose of warfarin can not be overstated – it is a difficult but important challenge. Both under- or over-anticoagulation can be fatal. A ‘correct’ dose of warfarin is one which results in maintaining an ‘in range’ international normalized ratio (INR) for the individual patient.
Medical research has already determined that polymorphisms in the VKORCI and the cytochrome P-450 2C9 (CYPC29) genes are known to increase sensitivity to warfarin and decrease the dose required to achieve optimal anticoagulation.
To further explore the impact of these two genes on warfarin sensitivity Michael Stein of Vanderbilt University (TN, USA) and his coworkers genotyped 297 patients starting warfarin therapy. They examined the relationship between the genes and time to first INR, time to first INR reading above 4, time spent above the therapeutic INR range, INR response over time and warfarin dose required.
They found that patients with the VKORC1 A/A haplotype were a significant 2.38 times more likely to achieve a therapeutic INR within 28 days of treatment than patients with the nonA/nonA haplotype. The CYP2C9 genotype was not associated with time to therapeutic INR but patients with the CYP2C9*2 and CYP2C9*3 variant alleles had a first INR result above 4 significantly earlier than patients with the wild-type allele CYP2C9*1.
Both the VKORC1 and CYP2C9 alleles predicted the warfarin dose required after the first 2 weeks, but the alleles did not predict the risk for bleeding complications in the patients.
The authors conclude, “Our results confirm the relationship between the CYP2C9 genotype and the response to warfarin that has been observed by others, but they also indicate that early in the course of anticoagulation the effect of the VKOPC1 haplotype is greater than that of the CYP2C9 genotype, and the presence of a VKORC1 A allele is associated with an accelerated and greater sensitivity to warfarin.”
Source: Schwarz UI, Ritchie MD, Bradford Y et al. Genetic determinants of response to warfarin during initial anticoagulation. N. Engl. J. Med. 358(10), 999–1008 (2008).
Curry ingredient may protect and repair the heart
Researchers at the Peter Munk Cardiac Centre of the Toronto General Hospital (Canada) found that when the herb was administered to a variety of mouse models with enlarged hearts, otherwise know as hypertrophy, this enlargement was reversed, heart function restored and scar formation reduced.
The herb has been known to have medicinal properties for sometime in traditional Indian and Chinese cultures, where it is used to reduce scar formation.
Curcumin works directly in the cell nucleus by suppressing histone acetylation – a critical player in the pathogenesis of hypertrophy and heart failure, which leads to abnormal unraveling of the chromosome under stress – and preventing excessive abnormal protein production.
“What is impressive about curcumin’s effects is its ability to shut off one of the major switches right at the chromosome source where the enlargement and scarring genes are being turned on,” says Peter Liu, Cardiologist in the Peter Munk Cardiac Centre and Scientific Director at the Canadian Institutes of Health Research – Institute of Circulatory and Respiratory Health. However, Liu cautions, “the beneficial effects of curcumin are not strengthened by excessive ingestion.” Liu says that since curcumin is a naturally occurring compound that is readily available at a low cost, it may be a safe and effective means of preventing heart failure in the future.
“Whether you are young or old; male or female; the larger your heart is, the higher your risk is for developing heart attacks or heart failure in the future. However, until clinical trials are done, it is not recommended for patients to take curcumin routinely. Take action today by lowering blood pressure, reducing cholesterol, exercising and healthy eating,” explains Liu.
Clinical trials of curcumin are due to follow shortly. A positive result could offer hope for millions of patients with heart enlargement in a relatively safe and inexpensive manner.
The compound is currently undergoing clinical trails for the treatment of pancreatic and colorectal cancer.
Source: Li HL, Liu C, de Couto G et al. Curcumin prevents and reverses murine cardiac hypertrophy. J. Clin. Invest. 118(3), 879–893 (2008); www.uhn.ca/index.asp
Heart failure trends in the elderly appear to be declining
That assumption has been partly challenged by new research from Duke University Medical Center (NC, USA). They have revealed that heart failure is actually declining among very elderly individuals, while the overall rates continue to rise.
“Heart failure is largely a disease of aging, so we were surprised by the findings,” says Lesley Curtis, a health services researcher at Duke and lead author of the study.
Curtis and colleagues conducted a retrospective cohort study on a 5% sample of Medicare beneficiaries’ claims between 1994 and 2003. They found that during that period, 622,789 patients were diagnosed with heart failure.
While the incidence of heart failure fell most sharply among those aged 80–84 years, from 57.5 to 48.4 per 1000 person years, it also rose from 17.5 cases to 19.3 cases per 1000 person-years among those aged 65–69 years old.
The study also found that the total number of Americans living with heart failure steadily increased over the 10-year study period, from approximately 140,000 to 200,000, with more men living with the disease than women.
Nearly 5 million individuals in the USA currently suffer from heart failure and even though mortality from the disease has fallen slightly, it remains a very serious problem. Nearly a third of those diagnosed with heart failure will die within 1 year and “that figure hasn’t budged over the last decade,” according to Curtis.
The authors go on to say, ‘Although the incidence of heart failure has declined somewhat during the past decade, modest survival gains have resulted in an increase in the number of patients living with heart failure.’ The result of this is that there must now be added emphasis on finding effective treatment strategies for heart failure.
Source: Curtis LH, Whellan DJ, Hammill BG et al. Incidence and prevalence of heart failure in elderly persons, 1994–2003. Arch. Intern. Med. 168(4), 418–424 (2008); www.mc.duke.edu
PL-3994 for CHF receives positive Phase I results
Drug: PL-3994
Patients (n):26
Company: Palatin Technologies, Inc. (NJ, USA)
Palatin Technologies, Inc. (NJ, USA) have announced the positive completion of a Phase I clinical trial of PL-3994 for the treatment of acute decompensated congestive heart failure (CHF). PL-3994 is a novel, long-acting natriuretic peptide receptor A (NPRA) agonist.
“We are excited to confirm that PL-3994 has the profile of biological activity in humans that was predicted from animal model data and that it was safe and well tolerated,” stated Trevor Hallam, Palatin’s Executive Vice President for Research and Development.
Currently in the USA CHF affects nearly 5 million people with 550,000 new cases of CHF diagnosed each year. Despite the treatment of CHF with multiple drugs, almost all CHF patients will experience at least one episode of acute CHF that requires treatment with intravenous medications in the hospital.
Hallam added, “CHF is the single most common cause of hospitalization in the USA for patients older than 65 years of age and is an area of high medical need for new therapies.”
The trial was a randomized, double-blind, placebo-controlled, single ascending dose study in 26 healthy volunteers who received the medication or placebo subcutaneously. The evaluations included safety, tolerability, pharmacokinetics and several pharmacodynamic end points, including levels of cyclic guanosine monophosphate (cGMP), a natural messenger nucleotide.
Data analysis is ongoing and will be submitted for presentation when the analysis is complete.
Source: www.palatin.com
Drugs to treat arthritis may concurrently be protecting against heart disease
According to recent research, patients affected by rheumatoid arthritis (RA) are at risk of suffering from a heart attack or stroke up to 10 years earlier than patients without the disease. However, the anti-inflammatory drugs used to treat RA may well be concurrently preventing heart disease progression.
People affected by RA, which causes pain, swelling, stiffness and loss of function in the joints, face a greater risk of heart disease, since the disease also affects the arteries, resulting in hardening.
An international team, led by Antonio Naranjo of the University of Las Palmas de Gran Canaria (Spain) and colleagues in Argentina, Europe and the USA, analyzed data from the Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) study. From this study, including 4363 patients from 48 sites in 15 countries, the team examined the causes and effects of RA, as well as the potential benefits of medications.
Previous studies have demonstrated that treating RA with disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, may reduce this risk.
Naranjo and colleagues found that risk, when adjusted for other variables such as age, sex, disease activity and traditional risk factors, such as lack of exercise, smoking, diabetes and high cholesterol levels, correlated strongly with the use of drugs to treat RA. Taking methotrexate – the most widely used DMARD – for just 1 year for example was found to be associated with an 18% reduction in risk of heart attack and an 11% decrease in risk of stroke, the researchers say.
“Our study provides further support of the influence of both traditional and RA-specific risk factors in the development of cardiovascular events, especially heart attack,” the researchers conclude. “As assessed by this study, the risk was lower with the prolonged use of methotrexate, sulfasalazine, glucocorticoids, leflunomide and TNF-blockers.”
Source: Naranjo A, Sokka T, Descalzo MA et al. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res. Ther. 10(2), R30 (2008) (Epub ahead of print).