Pneumococcal disease: A red flag in heart disease management

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

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 CHD, the leading cause of death worldwide.

In a 2000 study, Daniel M. Musher, MD, and colleagues brought a possible link between pneumococcal disease and CHD to the medical community’s attention. Source: Michael Spratt

“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, and a Cardiology Today Editorial Board member.

“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 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 Cardiology Today. “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 HF; eight had new-onset AF or ventricular tachycardia, with six of these patients also having new chronic HF; and 13 had newly diagnosed or worsening chronic HF.

William Schaffner

“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 Schaffner, MD, president, NFID, and chair, department of preventive medicine at Vanderbilt University, 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 CV system.”

Conflicting data, unflinching resolve

In May, 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 told Cardiology Today. “The logic of the study goes not only will the vaccine protect against pneumonia, which could cause stress, but 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 affect [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 that “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 practice set up for administering a vaccine, their role in whether their patients are vaccinated should still not be underestimated, Rehm said.

Susan Rehm

“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:

• Those 65 years of age and older.
• Adults aged 19 to 64 years who have asthma or smoke cigarettes.
• Everyone 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.

Joseph Alpert

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 V. Lancet Infect Dis. 2010;10:83-92.
• For Facts About Pneumococcal Disease, visit the National Foundation of Infectious Diseases website here. Accessed October 11, 2010.
• Madjid M. JAMA. 2010;303:1751-1752.
• Musher D. Clinical Infectious Diseases. 2007;45:158-165.
• Musher D. Medicine. 2000;79:210-221.
• Tseng H. JAMA. 2010;303:1699-1706.