The heart’s own immune cells can help it heal

The heart holds its own pool of immune cells capable of helping it heal after injury, according to new research in mice at Washington University School of Medicine in St. Louis.

Most of the time when the heart is injured, these beneficial immune cells are supplanted by immune cells from the bone marrow, which are spurred to converge in the heart and cause inflammation that leads to further damage. In both cases, these immune cells are called macrophages, whether they reside in the heart or arrive from the bone marrow. Although they share a name, where they originate appears to determine whether they are helpful are harmful to an injured heart.

In a mouse model of heart failure, the researchers showed that blocking the bone marrow’s macrophages from entering the heart protects the organ’s beneficial pool of macrophages, allowing them to remain in the heart, where they promote regeneration and recovery. The findings may have implications for treating heart failure in humans.

The study is now available in The Proceedings of the National Academy of Sciences Early Edition.

“Researchers have known for a long time that the neonatal mouse heart can recover well from injury, and in some cases can even regenerate,” said first author Kory J. Lavine, MD, PhD, instructor in medicine. “If you cut off the lower tip of the neonatal mouse heart, it can grow back. But if you do the same thing to an adult mouse heart, it forms scar tissue.”

This disparity in healing capacity was long a mystery because the same immune cells appeared responsible for both repair and damage. Until recently, it was impossible to distinguish the helpful macrophages that reside in the heart from the harmful ones that arrive from the bone marrow.

The new research and past work by the same group – led by Douglas L. Mann, MD, the Tobias and Hortense Lewin Professor of Medicine and cardiologist-in-chief at Barnes-Jewish Hospital – appear to implicate these immune cells of different origins as responsible for the difference in healing capacity seen in neonatal and adult hearts, at least in mice.

“The same macrophages that promote healing after injury in the neonatal heart also are present in the adult heart, but they seem to go away with injury,” Lavine said. “This may explain why the young heart can recover while the adult heart can’t.”

Because they are interested in human heart failure, Lavine and his colleagues developed a method to progressively damage mouse cardiac tissue in a way that mimicked heart failure. They compared the immune response to cardiac damage in neonatal and adult mouse hearts.

The investigators found that the helpful macrophages originate in the embryonic heart and harmful macrophages originate in the bone marrow and could be distinguished by whether they express a protein on their surface called CCR2. Macrophages without CCR2 originate in the heart; those with CCR2 come from the bone marrow, the research showed.

Lavine and his colleagues asked whether a compound that inhibits the CCR2 protein would block the bone marrow’s macrophages from entering the heart.

“When we did that, we found that the macrophages from the bone marrow did not come in,” Lavine said. “And the macrophages native to the heart remained. We saw reduced inflammation in these injured adult hearts, less oxidative damage and improved repair. We also saw new blood vessel growth. By blocking the CCR2 signaling, we were able to keep the resident macrophages around and promote repair.”

Some CCR2 inhibitors are being tested in phase 1 and 2 clinical trials for treating rheumatoid arthritis. But before these drugs can be evaluated in people with heart failure, more work must be done to find out whether the same mechanisms are at work in human hearts, according to the researchers.

“We have identified similar immune cell subtypes that are present in the human heart,” Lavine said. “We need to find out more about their roles in heart failure in patients and understand more about how macrophages that reside in the heart promote repair.”

http://www.medicalnewstoday.com/releases/284750.php

 

 

Heightened risk of anxiety, depression among women after heart attack

A new study by researchers from Lithuania claims women are more likely to experience anxiety and depression following a heart attack than men. Furthermore, patients with depression may be at much higher risk of death in the 6 months after a heart attack than those without depression.

 

Study author Prof. Pranas Serpytis and colleagues presented their findings at the annual meeting of the Acute Cardiovascular Care Association – a part of the European Society of Cardiology – in Geneva, Switzerland.

To reach their findings, the team analyzed 160 patients who were admitted to the Vilnius University Hospital Santariskiu Clinics in Vilnius, Lithuania, with a heart attack.

The researchers interviewed patients around 1 month after their heart attack to gather demographic information, such as age, sex education and marital status, and to determine whether they had a history of mental illness.

The team also collected clinical information from the patients – such as whether they had experienced a heart attack before and whether they had a history of high blood pressure or diabetes – and determined if they had any other risk factors for cardiovascular disease, including smoking and lack of physical activity.

The Hospital Anxiety and Depression Scale (HADS) was used to assess patients. Those who had a score of 0-7 had nodepression or anxiety, a score of 8-10 indicated possible depression and anxiety, while a score of 11 or more suggested mild to moderate levels of depression and anxiety.

The risks of anxiety, depression and death after heart attack

Almost 25% of patients were depressed, the researchers say, and 28.2% of these had used antidepressants.

The team found, however, that women were more likely to be depressed and anxious than men after a heart attack. Men had an average depression score of 6.87, while women’s average score was 8.66. For anxiety, men had an average HADS score of 7.18 and women had an average score of 8.20.

The researchers say that further studies are needed to determine why women appear to be at higher risk of anxiety and depression following a heart attack than men.

Commenting on this finding, Prof. Serpytis says:

“Women are misrepresented in many clinical studies on myocardial infarction (heart attack) even though they often have worse outcomes. Our study shows that women are more likely to develop anxiety and depression after myocardial infarction than men but until now this issue has been largely unnoticed.

Clinicians should assess myocardial infarction patients, particularly women, for anxiety and depression so that timely treatment can be started.”

Earlier this year, Medical News Today reported on a study suggesting the reverse effect – that depressed women are at higher risk of heart attack.

The researchers of this latest study also found that patients with depression following a heart attack were almost six times more likely to die in the 6 months after a heart attack, compared with patients who were not depressed.

“Major depression follows myocardial infarction in approximately 18% of cases and is an important predictor of disability and poor quality of life in the year post-myocardial infarction,” notes Prof. Serpytis.

“The increased risk of death in patients with depression persists up to 18 months after the myocardial infarction. But despite the fact that post-myocardial infarction depression is common and burdensome, the condition remains under-recognised and undertreated.”

Smoking increases anxiety risk, while lack of physical activity linked to depression

Furthermore, the team found an increased risk of anxiety among patients who smoked; the average HADS score for anxiety among smoking patients was 10.16, compared with an average score of 7.3 for patients who had never smoked and 4.55 for patients who stopped smoking more than 2 years before.

No link was found between smoking and depression after a heart attack, the researchers say.

However, a small link was found between lack of physical activity and depression. The 64% of patients who were physically inactive had an average HADS depression score of 8.96.

Commenting on the team’s overall findings, Prof. Serpytis says:

“Our study suggests that encouraging patients to quit smoking and increase their physical activity levels should reduce their risks of anxiety and depression after myocardial infarction. More research is needed on the links between myocardial infarction and mental health problems.”

MNT recently reported on a study by researchers from Duke University Medical Center in Durham, NC, claiming theeffects of mental stress on the heart differ between men and women.

Written by Honor Whiteman

http://www.medicalnewstoday.com/articles/284082.php

 

 

Genetic test reveals risk of atrial fibrillation and stroke

Many of those who are genetically predisposed to develop atrial fibrillation, which dramatically raises the risk of stroke, can be identified with a blood test. This is shown by new research from Lund University in Sweden.

The number of people affected by atrial fibrillation is rising rapidly, partly as a result of the ageing population.

Over recent years, a research group at Lund University in Sweden, working with other universities and hospitals in Europe and the USA, has identified twelve genetic variants in the human genome that increase the risk of atrial fibrillation. The research group has now studied the possible clinical benefits of a DNA test:

“One in five people have a genetic weakness that means they have twice as high a risk of developing atrial fibrillation as those with a low genetic risk. This genetic risk is therefore one of the strongest risk factors for atrial fibrillation that we know of in people without overt cardiac disease. It increases the risk as much as high blood pressure, for example”, said Olle Melander, Professor of Internal Medicine, and Gustav Smith, Associate Professor in Cardiology, both from Lund University.

Since the symptoms of atrial flutter can be weak and unclear, they are sometimes difficult to pick up. However, even those with weak or absent symptoms of atrial flutter are at significantly higher risk of stroke.

“In patients who are suspected of having temporary but recurrent episodes of atrial fibrillation, or in people with high blood pressure, it can be important for doctors to look at their genetic predisposition using a blood test. The test can give guidance as to how often and how intensively doctors need to screen for presence of atrial fibrillation in these individuals. We also consider that more widespread treatment of high blood pressure may be justified in those with a high genetic risk of atrial fibrillation”, explained Professor Melander.

Patients already diagnosed with atrial fibrillation were also studied, and the researchers observed that if they had the risk genes, their risk of stroke was increased by a further 70-80 per cent.

If an individual with atrial fibrillation is regarded as having a sufficiently high stroke risk, lifelong treatment with anticoagulant drugs such as warfarin is required in order to lower the risk.

“There are also benefits of checking the genetic risk of those who have already been diagnosed with atrial fibrillation. The test makes it easier to correctly assess whether anticoagulant medication is necessary to prevent stroke, especially for those under 65”, said Olle Melander.

The research data was taken from a long-term follow-up of 27 400 participants in a population study.

“The present results are one of several examples of how genetics research is not only an effective way of identifying new disease mechanisms, but can also have clinical applications and help doctors and patients to decide on the right tests and treatment”, said Olle Melander.

http://www.medicalnewstoday.com/releases/283463.php

 

 

Inflammation may be the reason high blood sugar levels damage blood vessels

Inflammation may be the reason high blood sugar levels damage blood vessels, raising the possibility that anti-inflammatory medications might someday be used to lower the risk of blood vessel disease in people with diabetes, according to a study presented at the American Heart Association’s High Blood Pressure Research Scientific Sessions 2014.

“These findings may explain why good blood sugar control is not sufficient to avoid the development of diabetes-induced cardiovascular diseases,” said Carlos F. Sánchez-Ferrer, M.D., Ph.D., study author and professor of pharmacology at the Universidad Autónoma de Madrid, Spain. “We need to find new medications focused on reducing inflammation.”

Using cultured smooth muscle cells from the main human artery (aorta), researchers found:

• In the absence of inflammation, excess glucose in the culture fluid didn’t enter the cells.
• When extra glucose was forced into the cells, no harm was done in the absence of inflammation.
• When the inflammation-stimulating protein interleukin-1 (IL-1) was introduced, more glucose entered the cells.
• With IL-1, the glucose entering the cells was metabolized via chemical pathways that spur escalating inflammation, overwhelming the cells’ ability to counteract it.
• In the presence of the anti-inflammatory drug anakinra, which blocks the activity of IL-1, the deleterious changes didn’t occur.

“We need to reduce the inflammatory environment associated with diabetes,” Sánchez-Ferrer said. “Changes in life-style, such as physical exercise and weight reduction, are important not only because they reduce blood sugar but because they reduce inflammation.”

The researchers plan to test whether the effect is similar in cultured cells from the lining of blood vessels and explore the blood sugar/inflammation connection in animals.

http://www.medicalnewstoday.com/releases/282447.php

 

Lack of rehab programs leaves cardiac patients underserved globally

Rehabilitation programs must become an integral part of cardiac care to significantly reduce the burden of living with heart disease, one of the most common chronic diseases and causes of death globally, according to York University Professor Sherry Grace.

“Cardiac rehabilitation is a cost-effective program offering heart patients exercise, education and risk reduction,” says Grace, noting that participation results in 25 per cent less death, lower re-hospitalization rates and better quality of life.

Despite these benefits, cardiac rehabilitation is vastly underused, particularly compared with costly revascularization and medical therapy, according to the review Grace conducted with Karam Turk-Adawi in the Cardiovascular Rehabilitation & Prevention Unit, University Health Network (UHN), and Dr. Nizal Sarrafzadegan, director of Isfahan Cardiovascular Research Center at Isfahan University of Medical Sciences in Iran.

“Cardiac rehabilitation services are insufficiently implemented, with only 39 per cent of countries providing any,” says Grace.

Heart disease has become an epidemic in low-income and middle-income countries (LMICs), and cardiac rehab can reduce the socio-economic impact of the disease by promoting return to work and reducing premature mortality, notes to Grace, who is also the director of research at the GoodLife Fitness Cardiovascular Rehabilitation Unit at the UHN.

“If supportive health policies, funding, physician referral strategies and alternative delivery modes are implemented, we could reduce the ratio from one cardiac rehab program per 6.4 million inhabitants in a middle income country like Paraguay, to the one program per 102,000 available in the US, a high income country,” adds Grace.

Low-income countries such as Afghanistan, Bangladesh and Kenya have one rehab program each for their entire population.

The article, Global availability of cardiac rehabilitation, published online at Nature Reviews Cardiology, indicates that while 68 per cent of high-income countries have cardiac rehabilitation, only 23 per cent of LMICs do, despite the fact that 80 per cent of deaths from heart disease occur in these countries.

http://www.medicalnewstoday.com/releases/279686.php

Picture courtesy to www.docstoc.com

 

 

 

One in five people with heart conditions stop having sex, UK survey

Sex is impossible for a fifth of people with heart conditions, according to new statistics released by the British Heart Foundation (BHF).

The BHF’s Heart Matters magazine polled over 1,500 people with heart conditions (1) and found 32 per cent had sex less often, and 19 per cent have stopped having sex completely as a result of their heart condition. One in five respondents said they were worried about having a heart attack or cardiac arrest during sex.

Over 7 million people in the UK suffer from heart and circulatory conditions (2). Based on the survey results, the BHF estimates that issues with sex could mar the lives of over one million people.

It isn’t just the physical effects that are blighting peoples’ sex lives – 14 per cent said they had lost interest in sex because of the emotional impact of their heart condition, and 5 per cent said scarring from an operation made them feel sexually unattractive.

36 year old Martin Tailford, who on Christmas day 2011 had a heart attack and has since had difficulty having sex with his wife Louise, said:

“After my heart attack sex wasn’t natural, it required a lot more planning. I couldn’t spontaneously have sex. I needed to think what to wear to cover up the scars and bruises.

“Sex isn’t what you base a relationship on, but it is really important. My heart attack had put a strain on Louise, and not being able to be physically close to her really took its toll on our relationship. I would advise people in my position to get help as soon as they can, and not be disappointed if things don’t go well at first. It takes time.”

But the BHF’s survey revealed people aren’t getting this help. 30 per cent of people have not discussed the issue with anyone, including their doctor. Eight per cent would have liked to access professional help but couldn’t get any.

The BHF is urging heart patients and GPs to talk openly about issues around sex, so treatment and support can be provided.

Doireen Maddock, Senior Cardiac Nurse at the BHF, said:

“Sex is a hugely important part of life, but isn’t getting the attention it deserves in the consultation room. We’re hearing loud and clear from Heart Matters readers that they need better support and information on how to deal with issues affecting their sex lives.

“Problems like erectile dysfunction can often be tackled and rectified, but the first hurdle is identifying people who need that help. We’d like patients to feel comfortable and empowered to raise these issues, and for the NHS to proactively offer support in this area to everyone who needs it.”

For information and support visit bhf.org.uk/sex

http://www.medicalnewstoday.com/releases/278654.php

 

 

 

FDA approves droxidopa for neurogenic orthostatic hypotension

Droxidopa, a prodrug that is converted into norepinephrine, has been approved for the treatment of patients with neurogenic orthostatic hypotension, a rare, chronic, and often debilitating condition associated with Parkinson’s disease, multiple system atrophy, and pure autonomic failure, the Food and Drug Administration announced on Feb 18.

The approval is based on two clinical trials of people with NOH, who, over 2 weeks of treatment, reported improvements in dizziness, light-headedness, feeling faint, “or feeling as if they might black out,” compared with those taking a placebo, the FDA said in a statement announcing the approval. The most common adverse events reported by patients in the studies were headache, dizziness, nausea, hypertension, and fatigue.

The approval is an accelerated approval, which enables the FDA to approve a drug for a serious disease with few treatment options, based on data showing that the treatment has an effect on a clinical measure that is considered “reasonably likely” to predict longer-term benefit. In the case of droxidopa, approval was based on short-term relief of dizziness. The manufacturer, Chelsea Therapeutics, is required to conduct a postmarketing study to confirm the drug’s benefits.

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Droxidopa is “a synthetic catecholamine that is directly converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE in the nervous system, both centrally and peripherally,” according to the company, which will market the drug under the trade name Northera.

“There are limited treatment options for people with NOH, and we are committed to helping make safe and effective treatments available,” Dr. Norman Stockbridge, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research, said in the statement. People with NOH “are often severely limited in their ability to perform routine daily activities that require walking or standing,” he added.

The prescribing information states that droxidopa is indicated for “the treatment of orthostatic dizziness, light-headedness, or the ‘feeling that you are about to black out’ in adult patients with symptomatic neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure [Parkinson’s disease (PD), multiple system atrophy, and pure autonomic failure], dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.”

The indications and usage statement also adds that effectiveness past 2 weeks “has not been established,” and that the “continued effectiveness of Northera should be assessed periodically.”

The prescribing information includes a boxed warning about the risk of supine hypertension, and recommends that supine blood pressure be monitored before and during treatment, and more often when doses are increased – and that elevating the head of the bed reduces the risk of supine hypertension.

At a meeting on Jan. 14, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 16 to 1 to recommend approval. In the FDA’s briefing documents filed prior to the meeting, the agency did not support approval of the drug, for reasons that included a lack of evidence indicating the drug had a durable effect, as well as safety issues.

Until the approval of droxidopa, the only drug approved for symptomatic NOH was midodrine, a vasoconstrictor that was approved in 1996. But midodrine may soon be off the market because postmarketing studies have failed to provide convincing evidence that treatment improves symptoms, according to the FDA’s briefing documents for the droxidopa panel meeting. Midodrine was approved on the basis of a surrogate endpoint – standing systolic blood pressure – which was considered “reasonably likely” to predict symptomatic benefit, but several postmarketing studies have failed to show that the drug is beneficial, despite its effect on increasing blood pressure.

NOH affects almost 300,000 people in the United States and European Union, according to Chelsea.

A statement on the approval issued by Chelsea said the company had a “preliminary” agreement with the FDA to conduct a postmarketing study to evaluate the clinical effects of droxidopa, which would be a multicenter, placebo-controlled, randomized study of about 1,400 patients enrolled over 6 years.

http://www.ecardiologynews.com/single-view/fda-approves-droxidopa-for-neurogenic-orthostatic-hypotension/138cf2a757264c256e82661ba60a3859.html

 

 

 

Successful anti-TNF therapy may cancel excess coronary risk in RA

SAN DIEGO – Rheumatoid arthritis patients with a good response to tumor necrosis factor inhibitor therapy when assessed roughly 5 months into treatment had an acute coronary syndrome risk during the next 2 years that was no different than that of the matched general population in a large, Swedish national registry study.

“We could see that the risk of acute coronary syndrome in the TNF inhibitor–exposed population was doubled in the first year compared to the general population. But all this increased risk was carried by patients with a moderate or nonresponse to therapy. We saw no difference in risk between the general population and patients with a good response to treatment. My belief is that this benefit is not due to the TNF inhibitor as such, but rather it’s the control of inflammation that is crucial,” Dr. Lotta Ljung said at the annual meeting of the American College of Rheumatology.

‘Good response’ was defined in this study via the EULAR response criteria: that is, a greater than 1.2-point improvement in the widely used Disease Activity Score 28 (DAS28) over baseline to a score of 3.2 or less at the 5-month evaluation.

Dr. Ljung, a senior consultant in rheumatology at Umea (Sweden) University Hospital, presented two analyses drawn from the Swedish Biologics Register, a national registry that captures 90% of all Swedes on biologic therapy for rheumatoid arthritis (RA). The study population included 7,704 RA patients with no history of ischemic heart disease when they started on their first TNF inhibitor during 2001-2010. They were matched by age, gender, and location to 23,112 RA patients who never took a biologic agent and to a second matched control group comprised of 38,520 individuals in the general population.

The crude incidence rate of acute coronary syndrome (ACS) in patients actively on TNF inhibitor therapy throughout follow-up was 5.7 events per 1,000 person-years, compared with 8.6 per 1,000 in biologic-naive RA patients and 3.3 per 1,000 in the matched general population.

In a fully adjusted Cox multivariate regression analysis factoring in socioeconomic variables, RA duration, joint surgery, and baseline atherosclerotic disease and other comorbid conditions, patients on anti-TNF therapy had a highly significant 27% reduction in ACS risk, compared with biologic-naive RA patients.

Nonetheless, patients on TNF inhibitor therapy remained at an adjusted 1.5-fold increased risk of ACS, compared with general population controls. However, this was significantly lower than the 2.3-fold elevated risk in biologic-naive RA patients.

In a separate analysis, the investigators took a closer look at the Swedish Biologics Register subgroup of the 4,931 RA patients on anti-TNF therapy for whom EULAR response data 5 months into treatment were available. Thirty-eight percent of these patients had a EULAR good response, 37% had a moderate response, and 25% had no response.

During 2 years of follow-up starting at the time of the EULAR response evaluation, the crude incidence rate of ACS among all TNF inhibitor–exposed RA patients, with close to 8,600 person-years of follow-up, was 6.9 cases per 1,000 person-years, compared with 3.4 per 1,000 among the matched general population controls. In an adjusted multivariate regression analysis, the ACS risk was 1.94-fold greater in moderate responders to anti-TNF therapy than in the general population and 2.53-fold greater in the nonresponders, but not significantly different between good responders and controls.

In addition, patients with an erythrocyte sedimentation rate (ESR) below 20 mm/hour at the time of their EULAR response evaluation had a subsequent 66% lower 1-year risk of ACS than did those with a higher ESR. And patients with a DAS28 remission at the 5-month evaluation – that is, a DAS28 below 2.6 – had a 79% lower ACS risk than did those with a DAS28 of 2.6 or above.

“This is dramatic,” Dr. Ljung said in an interview. “I think it’s the first time we see a population in our RA cohorts that doesn’t have any proven cardiovascular risk increase compared with the general population. But it raises additional questions, of course, such as who are these patients who receive the good response: Is it due to factors related to their disease or background that gives them the opportunity to have the good response? We adjusted for a number of factors, but still …”

She added that these studies contain two key take-home messages for rheumatologists: “I think the first thing for us to do is to treat our patients’ inflammation perfectly using traditional and biologic DMARDs. And the second thing is to be more aware of the traditional risk factors and start modifying those more aggressively for our patients.”

The Swedish Biologics Register is funded by the Swedish Rheumatology Association, with support from half a dozen pharmaceutical companies. Dr. Ljung disclosed ties with AbbVie and Bristol-Myers Squibb.

http://www.ecardiologynews.com/single-view/successful-anti-tnf-therapy-may-cancel-excess-coronary-risk-in-ra/b5c011441103b562af236684c1920cf3.html