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Statins and renin-angiotensin system inhibitor combination treatment to prevent cardiovascular disease
Hae-Young Lee1, Ichiro Sakuma, Sang-Hyun Ihm
1Division of Cardiology, Seoul National University College of Medicine.
Insights
Combined statin and renin-angiotensin system (RAS) inhibitor therapy effectively manages cardiovascular disease (CVD) risk factors like hypercholesterolemia and hypertension. This approach improves insulin resistance and endothelial dysfunction, offering synergistic benefits beyond monotherapy.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Metabolic Disorders
Background:
- Hypercholesterolemia and hypertension are key cardiovascular disease (CVD) risk factors, with synergistic negative impacts on insulin resistance (IR) and endothelial dysfunction.
- Unregulated renin-angiotensin system (RAS) significantly contributes to atherosclerosis and hypertension, and current antihypertensive strategies often fail to fully mitigate residual CVD risk.
- While statins reduce CVD risk, they can induce IR and increase type 2 diabetes mellitus risk, whereas RAS inhibitors improve endothelial dysfunction and IR.
Purpose of the Study:
- To investigate the combined effects of statins and RAS inhibitors on cardiovascular risk factors.
- To explore the synergistic mechanisms underlying the combined therapy's impact on IR and endothelial dysfunction.
- To evaluate the potential of combined statin and RAS inhibitor therapy in managing complex patient populations.
Main Methods:
- Review of experimental studies and clinical data on statin and RAS inhibitor therapies.
- Analysis of the interplay between hypercholesterolemia, RAS, IR, and endothelial dysfunction.
- Comparison of monotherapy versus combined therapy outcomes in relevant patient groups.
Main Results:
- Combined statin and RAS inhibitor therapy demonstrates additive/synergistic effects on improving endothelial dysfunction and IR.
- This combination therapy effectively lowers cholesterol and blood pressure more than monotherapy.
- The therapeutic benefits are mediated through both distinct and interconnected biological pathways.
Conclusions:
- Combined statin and RAS inhibitor therapy offers significant advantages over monotherapy for patients with hypertension and hypercholesterolemia.
- This combined approach is crucial for optimizing management strategies in patients with multiple CVD risk factors, including diabetes, metabolic syndrome, and obesity.
- Further research into combined therapy is warranted to fully elucidate its role in preventing CVD.
Abstract:
Hypercholesterolemia and hypertension are common risk factors for cardiovascular disease (CVD). Updated guidelines emphasize target reductions of overall cardiovascular risks. Experimental studies have shown reciprocal relationships between insulin resistance (IR) and endothelial dysfunction. Hypercholesterolemia and hypertension have a synergistic deleterious effect on IR and endothelial dysfunction. Unregulated renin-angiotensin system (RAS) is important in the pathogenesis of atherosclerosis and hypertension. Various strategies with different classes of antihypertensive medications to reach target goals have failed to reduce residual CVD risk further. Of interest, treating moderate cholesterol elevations with low-dose statins in hypertensive patients reduced CVD risk by 35-40% further. Therefore, statins are important in reducing CVD risk. Unfortunately, statin therapy causes IR and increases the risk of type 2 diabetes mellitus. RAS inhibitors improve both endothelial dysfunction and IR. Further, cross-talk between hypercholesterolemia and RAS exists at multiple steps of IR and endothelial dysfunction. In this regard, combined therapy with statins and RAS inhibitors demonstrates additive/synergistic effects on endothelial dysfunction and IR in addition to lowering cholesterol levels and blood pressure 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 CVD.
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