Are early clinical effects of cholesterol lowering mediated through effects on inflammation?
Version of Record online: 27 SEP 2002
Acta Physiologica Scandinavica
Volume 176, Issue 2, pages 147–150, October 2002
How to Cite
Olsson, A. G., Schwartz, G. G., Jonasson, L. and Linderfalk, C. (2002), Are early clinical effects of cholesterol lowering mediated through effects on inflammation?. Acta Physiologica Scandinavica, 176: 147–150. doi: 10.1046/j.1365-201X.2002.01017.x
- Issue online: 27 SEP 2002
- Version of Record online: 27 SEP 2002
- Received 5 February 2002, accepted 17 June 2002
- acute coronary syndrome;
- angina pectoris;
- low density lipoprotein;
In a randomized, double-blind trial in 3086 patients with unstable angina pectoris or non-Q wave myocardial infarction we investigated if 80 mg of atorvastatin daily could improve outcome of cardiovascular events during a short period of time (16 weeks) compared with placebo. Baseline LDL cholesterol was 3.2 mmol L−1 (124 mg dL−1) and decreased by 40% to 1.9 mmol L−1 (72 mg dL−1) during atorvastatin treatment. The primary endpoint, which was a composite of death, non-fatal acute myocardial infarction, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischaemia with objective evidence and requiring emergency rehospitalization occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group. The relative risk was0.84 and 95% confidence interval was 0.70–1.00 (P = 0.048). Thus for patients with acute coronary syndromes, lipid-lowering therapy with high dose atorvastatin reduces recurrent ischaemic events in the short-term. A possible mechanism behind this rapid clinical effect induced by statin treatment is on inflammatory processes. Recent studies strongly suggest that acute T-cell activation is involved in the pathogenesis of unstable angina. In another study we investigated whether circulating T cells showed signs of activation in patients with stable angina pectoris (SA). Systemic venous blood samples were taken from 38 men with SA and 42 healthy controls. The T-cell receptor expression was assessed by three-colour flow cytometry using monoclonal antibodies against CD3,CD4, CD8, CD25 and human leucocyte antigen (HLA)-DR. Soluble interleukin-2 receptor (sIL-2R) was measured as the circulating form in serum. Levels of circulating CD3+ and CD4+ T cells tended to be higher in patients compared with controls. Patients were also shown to have a significant increase in CD4+ T cells expressing the activation markers CD25 (P < 0.05) and HLA-DR (P < 0.01). Furthermore, serum levels of sIL-2R were significantly higher (P < 0.001) in patients than in controls. We also observed that the T-cell response was more pronounced in patients without simvastatin treatment (n = 18) compared with simvastatin-treated patients (n = 20). In conclusion, our findings indicate that a continuous immune system activation takes place in patients with chronic angina pectoris, predominantly involving proliferation of CD4+ T cells. Statin treatment seems to be able to decrease this inflammatory response.