Koh Kwang Kon, Sakuma Ichiro, Shimada Kazunori, Hayashi Toshio, Quon Michael J
Department of Cardiology, Gachon University Gil Medical Center, Incheon, Korea.
Gachon Cardiovascular Research Institute, Incheon, Korea.
Korean Circ J. 2017 Jul;47(4):432-439. doi: 10.4070/kcj.2016.0406. Epub 2017 Jul 26.
Hypercholesterolemia and hypertension are among the most important risk factors for cardiovascular (CV) disease. They are also important contributors to metabolic diseases including diabetes that further increase CV risk. Updated guidelines emphasize targeted reduction of overall CV risks but do not explicitly incorporate potential adverse metabolic outcomes that also influence CV health. Hypercholesterolemia and hypertension have synergistic deleterious effects on interrelated insulin resistance and endothelial dysfunction. Dysregulation of the renin-angiotensin system is an important pathophysiological mechanism linking insulin resistance and endothelial dysfunction to atherogenesis. Statins are the reference standard treatment to prevent CV disease in patients with hypercholesterolemia. Statins work best for secondary CV prevention. Unfortunately, most statin therapies dose-dependently cause insulin resistance, increase new onset diabetes risk and exacerbate existing type 2 diabetes mellitus. Pravastatin is often too weak to achieve target low-density lipoprotein cholesterol levels despite having beneficial metabolic actions. Renin-angiotensin system inhibitors improve both endothelial dysfunction and insulin resistance in addition to controlling blood pressure. In this regard, combined statin-based and renin-angiotensin system (RAS) inhibitor therapies demonstrate additive/synergistic beneficial effects on endothelial dysfunction, insulin resistance, and other metabolic parameters in addition to lowering both cholesterol levels and blood pressure. This combined therapy simultaneously reduces CV events when compared to either drug type used as monotherapy. This is mediated by both separate and interrelated mechanisms. Therefore, statin-based therapy combined with RAS inhibitors is important for developing optimal management strategies in patients with hypertension, hypercholesterolemia, diabetes, metabolic syndrome, or obesity. This combined therapy can help prevent or treat CV disease while minimizing adverse metabolic consequences.
高胆固醇血症和高血压是心血管疾病最重要的危险因素。它们也是包括糖尿病在内的代谢性疾病的重要促成因素，而这些代谢性疾病会进一步增加心血管疾病风险。更新后的指南强调有针对性地降低总体心血管疾病风险，但并未明确纳入同样会影响心血管健康的潜在不良代谢后果。高胆固醇血症和高血压对相互关联的胰岛素抵抗和内皮功能障碍具有协同有害作用。肾素 - 血管紧张素系统失调是将胰岛素抵抗、内皮功能障碍与动脉粥样硬化发生联系起来的重要病理生理机制。他汀类药物是预防高胆固醇血症患者心血管疾病的参考标准治疗方法。他汀类药物对心血管疾病的二级预防效果最佳。不幸的是，大多数他汀类药物治疗会剂量依赖性地导致胰岛素抵抗，增加新发糖尿病风险，并加重现有的2型糖尿病。普伐他汀尽管具有有益的代谢作用，但往往效力太弱，无法达到目标低密度脂蛋白胆固醇水平。肾素 - 血管紧张素系统抑制剂除了控制血压外，还能改善内皮功能障碍和胰岛素抵抗。在这方面，基于他汀类药物和肾素 - 血管紧张素系统（RAS）抑制剂的联合治疗除了能降低胆固醇水平和血压外，还对内皮功能障碍、胰岛素抵抗及其他代谢参数具有相加/协同的有益作用。与单独使用任何一种药物进行单一疗法相比，这种联合疗法能同时降低心血管事件的发生率。这是由多种独立和相互关联的机制介导的。因此，基于他汀类药物的治疗与RAS抑制剂联合使用对于制定高血压、高胆固醇血症、糖尿病、代谢综合征或肥胖患者的最佳管理策略非常重要。这种联合疗法有助于预防或治疗心血管疾病，同时将不良代谢后果降至最低。
