Hyperlipidemia as an Instigator of Inflammation: Inaugurating New Approaches to Vascular Prevention

1. Paul M Ridker, MD

+Author Affiliations

1. Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

1. Correspondence to:
   Paul Ridker, MD, Director, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, 900 Commonwealth Ave East, Boston, MA 02215. E-mailpridker@partners.org

For much of the past quarter century, 2 broadly competing scientific views have dominated translational research concerning atherogenesis and atherothrombosis. On one side has been a predominantly lipid-centric view in which low-density lipoprotein (LDL) cholesterol, a proven causal factor in atherosclerosis, has been viewed as the major if not sole determinant of disease initiation and progression. Pioneering descriptions of the role played by the LDL receptor in human disease and the remarkable success of statin therapy provide emblematic support for this scientific viewpoint and are milestones in the history of cardiovascular medicine.¹Ongoing research into agents that reduce proprotein convertase subtilisin/kexin type 9 (PCSK9) activity² or that inhibit the intestinal Niemann-Pick C1-like protein 1 (NPC1L1) cholesterol transporter³ represent current expressions of the established view that ever lower levels of LDL cholesterol are likely to be beneficial, and that pharmacologic inhibition of cholesterol on top of statin therapy might again transform medical practice. However, there are paradoxes in the LDL literature that have long puzzled investigators including observations that LDL cholesterol is only a modest predictor of vascular risk in the general population; that most myocardial infarction and stroke events occur among those with relatively low LDL cholesterol levels; that not all agents that reduce LDL cholesterol reduce vascular events; and that the relative risk reductions associated with statin therapy occur within weeks of drug initiation and are fully independent of the underlying level of LDL cholesterol.

Article on p 27

• • Molecular Cardiology

Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models

1. Enrico Ammirati, MD; et al.

+Author Affiliations

1. Clinical Cardiovascular Biology Centre, San Raffaele Scientific Institute and the Università Vita-Salute San Raffaele, Milan, Italy (E.A., D.C., M.B.)
2. Flow cytometry Resource Analytical Cytology Technical Applications Laboratory, San Raffaele Scientific Institute and the Università Vita-Salute San Raffaele, Milan, Italy (V.V., A.G.P.)
3. Clinical Immunology Unit, San Raffaele Scientific Institute and the Università Vita-Salute San Raffaele, Milan, Italy (A.A.M.)
4. Heart Transplantation Division, Ospedale Niguarda Ca' Granda, Milan, Italy (E.A.)
5. Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) Milan, Italy, Department of Cardiovascular Sciences, University of Milan Milan, Italy (M.D.M.)
6. Center for the Study of Atherosclerosis, Italian Society for the Study of Atherosclerosis Lombardia Chapter, Bassini Hospital Cinisello BalsamoMilan, Italy (L.G., F.P., K.G., S.T., G.D.N.)
7. Department of Pharmacological Sciences, Università degli Studi di Milano, Milan, Italy (A.L.C., G.D.N.)
8. Multimedica IRCCS, S.S. Giovanni, Milan (L.G., A.L.C.)
9. Heart Care Foundation, Florence, Italy (E.A., A.M.)

 

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Abstract

Background—Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of naïve CD4⁺T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4⁺T-cell subsets and atherosclerosis./.../