Inflammation as a residual risk post ACS
hypercholesterolemia, myocardial infarction, TA-65, impaired innate immunity, inflammation, infections, sepsis, platelet aggregation, coronary artery disease
HYPERCHOLESTEROLEMIA, MYOCARDIAL INFARCTION, ADVERSE EVENTS, INFLAMMATION, INFECTIONS, EVENTS, SEPSIS, CORONARY ARTERY DISEASE
Secondary prevention in patients who have undergone revascularisation after myocardial infarction aims to reduce their residual risk, predominantly by targeting hypercholesterolemia (with cholesterol-lowering agents) and platelet aggregation (with antiplatelet therapy). Recently, inflammation, as quantified by hsCRP, has been added to these determinants of residual risk. The CANTOS trial demonstrated that reducing inflammation in patients with coronary artery disease and elevated hsCRP (> 2 mg/l) reduced the rate of major adverse cardiovascular events [The major limitation of canakinumab in the CANTOS trial was the effect of IL-1β blockade on immunity. Patients in the treatment group had more infections, and a higher risk of dying from sepsis. However, our data shows that patients treated with TA-65 have no significant change in myeloid cells (monocytes and neutrophils) compared to placebo, suggesting they do not have impaired innate immunity. Indeed, their adaptive immunity appears to be enhanced, as indicated by an increase in the number of all lymphocyte subsets. An increase in lymphocyte count from 1600 to 1900 cells/µL (similar to what we have observed with TA-65 treatment in this study) correlates with a 50% reduction in the hazard ratio for both all-cause mortality and cardiovascular mortality in the large JAMA cohort study of 50,000 healthy Americans [In summary, the telomerase activator TA-65 appears to enhance adaptive immune cell numbers in the peripheral blood without negatively affecting innate immunity. We observed a trend towards reduced inflammation in patients following MI, and we hypothesise based on work by other groups that improved mitochondrial function in T lymphocytes leads to a reduction in cytokine generation and hence reduced inflammation. Clinically, there was no evidence for an increase in adverse events with TA-65 – in fact there were significantly fewer adverse events in the TA-65 group.