Pneumococcal disease: A red flag in heart disease management

Inflammation via infection cited for causing a coagulation cascade that can lead to myocardial infarction.

Pneumococcal disease, the leading cause of serious illness in children and adults worldwide, is leaving an irreparable mark on the lives of hundreds of thousands of Americans, as well as millions outside the US every year. Streptococcus pneumoniae, the common bacteria that initiates the disease, is the leading cause for bacterial pneumonia and can also lead to other conditions such as middle ear infection, meningitis and bacteremia.

For such widespread and, in some cases, deadly conditions, just a single dose of the pneumococcal polysaccharide vaccine has been proven to protect against the 23 types of S. pneumoniae bacteria responsible for causing more than 90% of all invasive pneumococcal disease cases in adults.

However, modern medicine is uncovering that vaccination may do more than prevent these infectious diseases, as pneumococcal disease may lead to chronic heart disease (CHD), the leading cause of death worldwide.

“The Centers for Disease Control and Prevention has been specifically targeting people with chronic conditions because we know that in the general population there is significant morbidity and mortality every year due to pneumococcal disease and people with chronic illnesses, like chronic heart disease, are at increased risk of complications caused by pneumococcal disease,” said Susan Rehm, MD, National Foundation for Infectious Diseases (NFID) medical director and vice chair of the department of infectious disease at Cleveland Clinic.

Establishing the link

By the end of 20th century, there was little known about the association between pneumococcal pneumonia and CHD because it had received relatively little examination in medical literature. Despite this, the connection between infection and atherosclerosis had already been suggested by researchers for many years, according to Joseph Alpert, MD, department of medicine, University of Arizona, Tucson.

“People have long been suggesting infection as an inciting factor in starting atherosclerosis,” Alpert said in an interview. “In fact, atherosclerosis probably starts with some inflammatory process, which could be a virus, an infection or an auto-immune condition. Then you have certain conditions that play into that inflammation, such as high cholesterol, hypertension, diabetes and genetic factors.”

The relationship between pneumococcal disease — one of the inflammation-inciting conditions — and CHD only began to receive attention in 2000 when Daniel M. Musher, MD, and colleagues published a study in Medicine. What had started as reporting on a series of patients with pneumococcal pneumonia turned into some of the first clues linking the two diseases. They found that five of the 100 admitted patients had acute myocardial events that they suspected were triggered by the physical stress of the pneumonia, whereas four patients had acute myocardial infarction (MI) and one had acute onset of atrial fibrillation without documented ischemia.

“I was initially surprised to see the number of patients that had MI at the time of admission. There just were no observations of this in earlier literature,” Musher, professor, department of medicine-infectious disease, Baylor College of Medicine, Houston, told Infectious Disease News. “Based on this data, I went ahead and did a confirmatory study on patients with pneumococcal pneumonia, carefully reviewing them as they came in. The number actually turned out to be a little higher than what was initially observed: 7% to 8% had MI, and another 8% had arrhythmias.”

These findings led Musher and fellow researchers to conduct what many cardiologists cite as the study that firmly established the connection between pneumococcal disease and CHD. This study, published 7 years after his initial findings, reported that of the 130 patients admitted during a 5-year period with pneumococcal pneumonia, 33 (19.4%) had at least one major cardiac event. Specifically, 12 had MI, of whom two also had arrhythmia and five had new-onset or worsening chronic heart failure (HF); eight had new-onset atrial fibrillation (AF) or ventricular tachycardia, with 6 of these patients also having new chronic HF; and 13 had newly diagnosed or worsening chronic HF.

“It seemed quite clear that severe inflammation of one place in the body was associated with increased inflammation in the coronary arteries, which led to acute MI,” Musher said.

For William A. Schaffner, MD, president, NFID, chair, department of preventive medicine at Vanderbilt University, and Infectious Disease News blogger, the findings from this study were particularly important in substantiating the connection between the two diseases. “I may be the last infectious disease doctor that has gotten on this train, simply because I hadn’t read all these studies and integrated them in my mind,” he said. “The findings presented in the 2007 study are part of the evidence that goes to validate this concept. It stands to reason, given that this is correct, that if we could prevent pneumococcal disease, we could prevent a stress and insult on the cardiovascular (CV) system.”

Conflicting data, unflinching resolve

In May of 2010, Tseng and colleagues published a study in JAMA that on first glance seemed to take the momentum out of the growing body of evidence confirming the link between pneumococcal disease and CHD. Among a cohort of men aged 45 to 69 years, the researchers concluded, receipt of pneumococcal vaccine was not associated with subsequent reduced risk for acute MI and stroke after accounting for baseline differences in participants who received vaccination vs. those who did not.

“This study essentially turned the coin over,” Schaffner said. “The logic of the study that goes not only will the vaccine protect against pneumonia, which could cause stress, but also I wonder if the vaccine itself will have a demonstrable role in reducing the occurrence of some pretty hard endpoints — MI and stroke. That’s a big question to ask of the vaccine, which is only supposed to prevent pneumonia. The researchers could not demonstrate an effect [on these diseases], and frankly; I’m not surprised. But it doesn’t negate in any way the importance of getting vaccinated to prevent the infectious illness.”

However, on second look, the study is more positive regarding the effect of pneumococcal vaccination than it may appear on initial read, Rehm said. “This large study said that vaccination with pneumococcal vaccine was not associated with MI or stroke. There have been concerns among physicians that giving a vaccination would provoke an inflammatory response that might result in stroke or heart attack,” she said. “This study showed that the vaccine does not stimulate stroke or heart attack.”

Alpert agreed. “The bottom line of this study is that it is perfectly safe to give the pneumococcal vaccination, even if the patient has heart disease,” he said. “In fact, it’s a good idea for patients to get vaccinated because if they develop pneumococcal pneumonia on top of their heart or lung disease, they often have a much more complicated course. Therefore, we’d like to protect them against having a severe bout of pneumococcal pneumonia.”

The cardiologist’s role

Even though most cardiologists may not have their practices set up for administering vaccines, their role in whether their patients are vaccinated should still not be underestimated, Rehm said.

“Because cardiologists see patients at risk, not only with chronic heart disease, but also with peripheral vascular disease, chronic pulmonary diseases and so on, they are excellently situated to identify people who might benefit from pneumococcal vaccination,” she said. “Having the ability to administer vaccines in one’s practice setting varies from place to place, but the education a cardiologist can provide to a patient is extremely important.”

“The cardiologist’s recommendation is especially important because of all the motivators to get people to accept vaccines, the specific doctor’s recommendation directly to the patient is the most compelling and produces the most results,” Schaffner said. “This would stimulate a terrific amount of vaccination.”

To help spot those most in need of a vaccination, the NFID has published a number of specific criteria that physicians should keep in mind when dealing with their patients. They include vaccinating:

• Those 65 years of age and older.
• Adults aged 19-64 years who have asthma or smoke cigarettes.
• Those 2 years of age and older with chronic medical conditions such as diabetes; heart, kidney, liver or chronic lung diseases; or alcoholism.
• Those whose immune systems have been weakened by such conditions as cancer or HIV infection.
• People without a functioning spleen, and those with sickle cell disease.
• Residents of chronic care or long-term care facilities.
• Children at 2, 4 and 6 months of age, followed by a booster dose at 12 to 15 months.
• Children aged 24 to 59 months who are at high risk for pneumococcal infection.

For Alpert, a cardiologist who recommends that all of his patients get vaccinated, pneumococcal vaccination is a necessity similar to vaccinations for the flu. “It is part of a standard primary care series of vaccinations,” he said. “Whatever the preventive measures are, people should definitely take them because, particularly as people get older and if they have heart or lung disease, these infections can be literally life-threatening.”

“It’s clear that pneumococcal disease is a regular hazard, particularly in people who have underlying heart disease. Vaccination against this disease is cheap, effective and a great preventive measure,” Schaffner said. “You can do an awful lot of good for your patients by making a simple and strong recommendation to be vaccinated.” – by Brian Ellis

For more information:

• Corrales-Medina VF. Lancet Infect Dis. 2010;10:83-92.
• Facts About Pneumococcal Disease. National Foundation of Infectious Diseases website. Accessed Oct. 11, 2010.
• Madjid M. JAMA. 2010;303:1751-1752.
• Musher DM. Clinical Infectious Diseases. 2007;45:158-165.
• Musher DM. Medicine. 2000;79:210-221.
• Tseng HF. JAMA. 2010;303:1699-1706.

Disclosures: Drs. Alpert, Musher and Schaffner have no relevant financial disclosures. Dr. Rehm is a member of advisory boards for Pfizer and Merck, and has spoken for Sanofi.

How aggressive should the ID specialist’s approach be at vaccinating those at risk for chronic heart disease?

The approach should be very aggressive

Very aggressive; and I would also add the influenza vaccine. When we think of pneumococcal vaccine, we should also think of influenza; when we think of influenza, we should also think of pneumococcal disease. They’re both respiratory infections and they operate somewhat similarly in terms of the effect on any underlying illness. Chronic heart disease would be one of many in the list that would justify it, but I think what’s special about chronic heart disease is that it’s so common, particularly in the developed world. So, we have lots of patients who have underlying heart disease, both structural and functional, that puts them at risk for cardiac complications related to pneumococcal infection. For the heart, the major things that we face are, No. 1, comprised of already compromised cardiac functions. The other possibility is of pneumococcal infection of the heart, and that can lead to some really nasty complications. So our recommendation, both here at Mayo and at the ACIP, is that patients who have underlying chronic cardiac disease are prime candidates to receive pneumococcal vaccine.

Now there’s a misconception; some practitioners misunderstand the recommendations and think, well you have to wait until they’re age 65 to immunize, and that’s not correct. Any adult of any age with chronic cardiac disease is a candidate to receive pneumococcal vaccine.

In addition, people don’t know the term “pneumococcal immunization” or “pneumococcal disease.” They don’t really know what that means. They think of it as a “pneumonia vaccine” or a “pneumonia disease.” This gets a little confusing because the vaccine does not protect against pneumonia. What it protects against are the complications of pneumonia. So, there does need to be a bit of education about that. There needs to be education about the risks and about the administration’s schedule of the vaccine. I know some practitioners, for example, put up on their practice’s website short monographs or information about what vaccines their patients should receive. Some have posters in their waiting room, or even video tapes that endlessly loop and talk about preventive care. So, there are lots of ways, and I think starting at the level of a physician’s office, to educate not only the physician and the physician’s staff, but also the patients that they’re privileged to care for.

Gregory A. Poland, MD, is director, Vaccine Research Group, Mayo Clinic. Disclosure: Dr. Poland has no relevant financial disclosures.

Vaccinating those at risk for heart disease is part of standard preventive health guidelines

We always advise the yearly influenza vaccine and a reasonably current pneumococcal vaccine. Elderly persons with heart failure or advanced coronary atherosclerosis or a history of stroke are at increased risk for death from pneumonia. Cardiologists do not store the vaccine in their office; it is the responsibility of the primary care physician to administer the pneumococcal vaccine to heart disease patients. In order to increase vaccination rates, we must simply remind patients and their primary care providers to get vaccinated against influenza every year, and against pneumococcal disease every 5 years.

Roger Blumenthal, MD, is professor of medicine at Johns Hopkins University. Disclosure: Dr. Blumenthal has no relevant financial disclosures.