Platelet Activation Seen as Key to Link Between MI and Community-Acquired Pneumonia

October 28, 2014

ROME, ITALY — A new study supports heightened platelet activation as a mechanistic link between community-acquired pneumonia (CAP) and MI but casts doubt on whether aspirin alone would be an effective measure for lowering the MI risk[1].

Researchers observed that patients with CAP who developed MI in the early days of hospitalization showed significant elevations in markers of platelet activation, including soluble-P selectin and soluble CD40 ligand, compared with CAP patients who did not develop MI.

In addition, these CAP patients with MI had significantly elevated levels of serum thromboxane B2 (TxB2), a marker of platelet formation of thromboxane A2. The researchers, led by Dr Robert Cangemi (Sapienza University of Rome, Italy), observed no significant differences in the MI rate among CAP patients taking 100 mg of aspirin daily and those not treated with aspirin, suggesting it "seems insufficient to inhibit thromboxane biosynthesis."

The group's report was published in the November 4, 2014 issue of the Journal of the American College of Cardiology.

MI Silent in Majority of Cases

In an editorial[2], Drs Carlos Santos-Gallego and Juan Badimon (Icahn School of Medicine at Mount Sinai, New York) home in on the clinical implications from the study.

"The main clinical take-home message is that patients with previous cardiovascular disease or severe CAP (both independently associated with MI) should be monitored daily with [high-sensitivity cardiac troponin T] hs-cTnT and electrocardiographic assessment to detect MI, especially during the first 2 days of hospitalization, because MI was asymptomatic and increased the risk for death," they write.

The editorialists note that more than 40% of the patients had increased concentrations of hs-cTnT without ECG changes, so the elevation in troponin is "probably not secondary to ischemia." Instead, the increase is possibly caused by stress-induced cardiomyopathy or other nonspecific toxic effects of cardiomyocytes, leading to biomarker leakage.

The study included 278 patients hospitalized for CAP who were followed until discharge.

Of these, 144 patients had elevated levels of hs-cTnT, defined as >0.014 µg/L. The majority of these patients had isolated elevations in hs-cTnT, and 31 patients had signs of MI, which was noted by increased hs-cTnT concentrations and ECG changes or symptoms. The MIs, of which 26 were non-ST-segment MIs, two were STEMIs, and three were fatal, occurred predominantly within 48 hours of presenting with pneumonia.

The patients who had elevations in hs-cTnT, with or without MI, were older and had a higher prevalence of chronic obstructive pulmonary disease, atrial fibrillation, renal failure, diabetes, and peripheral arterial disease. As noted, the baseline plasma levels of soluble CD40 ligand and soluble P-selectin, serum TxB2, and mean platelet volume were elevated in patients who developed signs of MI.

In a logistic regression analysis, which attempted to address the confounding baseline characteristics, these markers were all significant predictors of MI. In addition, a higher score on the pneumonia severity index and reduced ejection fraction were also independently associated with MI.

"Because MI was silent in the majority of cases, daily monitoring of troponins and electrocardiography is needed for detection," write Cangemi et al. "Platelet activation was significantly associated with MI, suggesting a role for platelets in triggering coronary thrombosis."

Do Other CV Risk Factors Play a Role?

Speaking with heartwire , Dr Jacob Udell (University of Toronto, ON), who has shown previously that a flu vaccination reduces the risk of cardiovascular disease, noted that majority of pneumonia cases are caused by viruses, a proportion of which is influenza or an influenzalike illness. The present study, with which he was not affiliated, was unable to discriminate between CAP caused by bacteria and CAP caused by viruses, but "it would have been interesting to see how many of the patients were admitted during influenza season."

Regarding the finding that platelet activation is a mediating factor between CAP and MI risk, Udell said the study is observational in nature. Given differences in the baseline characteristics, it might be that CAP patients with underlying disease are predisposed to MIs vs those CAP patients without preexisting cardiovascular risk factors.

"Until you randomize patients to pneumonia vs no-pneumonia and then follow them until you see who has an MI, you won't ever really figure this out," said Udell. "And nobody would do that." Still, despite the lack of a gold-standard, large randomized trial proving the cardiovascular benefits of an influenza vaccination, Udell has said he is a proponent of the flu shot based on the meta-analysis of smaller trials of cardiovascular risk reduction and its other health benefits.

Along with Dr Orly Vardeny (University of Wisconsin, Madison), Scott Solomon (Brigham and Women’s Hospital, Boston, MA), and Michael Farkouh (Peter Munk Cardiac Centre, Toronto, ON), Udell is preparing a study examining two different influenza vaccinations—the standard dose vs a high-dose trivalent vaccination—on cardiovascular outcomes. Like the study by the Italian researchers, he said their trial will also measure markers of inflammation and platelet activation to address the possible mechanisms between influenza, vaccination, and cardiovascular events and whether such mediators are modified by the different vaccinations.


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