Renin-angiotensin system inhibitor and statins combination therapeutics - what have we learnt?
Hypercholesterolemia and hypertension are the most common risk factors for cardiovascular disease (CVD). Updated guidelines emphasize target reduction of overall cardiovascular risks. Hypercholesterolemia and hypertension have a synergistic deleterious effect on insulin resistance and endothelial dysfunction. Unregulated renin-angiotensin system (RAS) is important in the pathogenesis of atherosclerosis. Statins are the most important in patients with hypercholesterolemia to prevent CVD by lowering low-density lipoprotein-cholesterol, improving endothelial dysfunction, and other anti-atherosclerotic effects. Unfortunately, statin therapy dose-dependently causes insulin resistance and increases the risk of type 2 diabetes mellitus. RAS inhibitors improve both endothelial dysfunction and insulin resistance in addition to blood pressure lowering. Further, cross-talk between hypercholesterolemia and RAS exists at multiple steps of insulin resistance and endothelial dysfunction. In this regard, combined therapy with statins and RAS inhibitors demonstrates additive/synergistic beneficial effects on endothelial dysfunction and insulin resistance in addition to lowering both cholesterol levels and blood pressure and it did reduce cardiovascular events when compared with either monotherapy in patients. This is mediated by both distinct and interrelated mechanisms. Therefore, combined therapy with statins and RAS inhibitors may be important in developing optimal management strategies in patients with hypertension, hypercholesterolemia, diabetes, metabolic syndrome or obesity to prevent or treat CVD.
Gachon University Gil Hospital, Division of Cardiology, Vascular Medicine and Atherosclerosis Unit , 774 Beongil 21, Namdongdaero, Namdong-Gu, Incheon , Korea +82 32 460 3683 ; +82 32 469 1906 ; kwangk@gilhospital.com.
Kwang Kon
KK
Koh
Ichiro
I
Sakuma
Toshio
T
Hayashi
Sang Hyun
SH
Kim
Wook-Jin
WJ
Chung
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007333:Insulin Resistance; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012306:Risk
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
cardiovascular disease; hypercholesterolemia; hypertension; renin–angiotensin system inhibitors; statins