Unusual CD4+CD28null T Lymphocytes and Recurrence of Acute Coronary Events
Giovanna Liuzzo, MD, PhD*,*,
Luigi M. Biasucci, MD*,
Graziana Trotta, MD*,
Salvatore Brugaletta, MD*,
Michela Pinnelli, MD*,
Giovanna Digianuario, MD*,
Vittoria Rizzello, MD*,
Antonio G. Rebuzzi, MD*,
Carlo Rumi, MD ,
Attilio Maseri, MD and
Filippo Crea, MD*
* Department of Cardiology, Catholic University, Rome, Italy
Department of Flow Cytometry Core Laboratory, Catholic University, Rome, Italy
Dipartimento Cardiotoracovascolare, Università "Vita e Salute," Milan, Italy.
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Figure 2 CD4+CD28null T-Cell Frequencies in Different Groups
Frequencies of CD4+CD28null T cells were determined by 2-color flow-cytometry. (A) The unstable angina (UA) patients were subgrouped according to the occurrence of both prior and further events during the 48 months of study observation. Group 1: 51 patients with the first-ever event; group 2: 30 patients with myocardial infarction and/or UA during the 24 months before study enrollment; group 3: 39 patients with further events during the 24 months of follow-up (death, myocardial infarction, UA), the majority of whom (85%) also had prior events; group 4: 67 patients with chronic stable effort angina (CSA). The CD4+CD28null T-cell frequency was significantly higher in group 3 than in the other groups (p < 0.001; Kruskal-Wallis test). (B) The UA patients were subgrouped according to the occurrence of events (none versus 2 or more) during the 24 months before the study enrollment independently of the prospective outcome. CD4+CD28null T-cell frequency was significantly higher in 63 patients with previous events than in 57 patients without previous events (p = 0.006). Data are presented as single data points. The dashed lines indicate CD4+CD28null T-cell frequencies  4% (90th percentile of distribution in 100 age-matched healthy subjects) and >10% (10-fold higher than the median value in healthy subjects). Blue, green, and red dots indicate patients with CD4+CD28null T-cell frequencies <4%, 4% to 10%, and >10%, respectively.
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Figure 3 CD4+CD28null T-Cell Frequencies According to the Number of Acute Coronary Events
In patients with unstable angina, CD4+CD28null T-cell frequency significantly increased according to the number of events occurring during the 24 months before the study enrollment: 1 versus 2 to 3 and 4 to 5 (p < 0.001; Kruskal-Wallis test). Data are presented as in Figure 2.
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Figure 4 CD4+CD28null T Cells and CRP
(A) CD4+CD28null T-cell frequency was significantly higher in patients with unstable angina (UA) and elevated C-reactive protein (CRP) levels (3 mg/l) than in patients with UA and low CRP levels (p < 0.001). Data are presented as in Figure 2. (B) In the overall population including UA and CSA patients, a statistically significant correlation was found between CD4+CD28null T-cell frequencies and CRP levels (r = 0.39; p < 0.001).
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Figure 5 Kaplan-Meier Cumulative Survival Plot According to CD4+CD28null T-Cell Frequency
The 24-month survival free of readmission for unstable angina, myocardial infarction, and death was significantly higher in patients with a percentage of CD4+CD28null T cells <4% (blue line) than in patients with CD4+CD28null T cells 4% (red line) as assessed by the log rank test (p = 0.004).
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Figure 6 Event Rate According to CD4+CD28null T-Cell Frequency and Statin Treatment
The event rate, at 24 months of follow-up, according to CD4+CD28null T-cell frequency (<4%, 4% to 10%, and >10%) and statin treatment was 15%, 30%, and 33% in patients treated with statins (p = 0.58) and 17%, 25%, and 64% in patients who never took statins (p = 0.003).
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