Vascular Biology Research Laboratory, Internal Medicine III, Hospital Clínico San Carlos, C/Martín Lagos s/n, 28040 Madrid, Spain.
Eur J Heart Fail. 2010 Sep;12(9):903-12. doi: 10.1093/eurjhf/hfq101. Epub 2010 Jul 2.
Although statins may provide potential therapeutic pathways for patients with heart failure with preserved ejection fraction (HFpEF), no studies have evaluated statins in combination with standard HF therapy, which would reflect clinical practice more closely. To address this question, we evaluated whether rosuvastatin added to a standard HF therapy provides additional improvement in cardiac structure and function in rats with hypertensive heart failure (SHHF).
Two-month-old SHHF rats were randomly assigned to four groups: (i) non-treated SHHF rats; (ii) rosuvastatin-treated SHHF rats; (iii) SHHF rats treated with quinapril plus torasemide plus carvedilol (considered as standard HF therapy); and (iv) SHHF rats treated with the combination of standard HF therapy and rosuvastatin. The administration of a standard anti-hypertensive HF therapy to SHHF rats for 17 months attenuated left ventricular (LV) chamber dilatation, cardiac hypertrophy, fibrosis, and inflammation compared with non-treated SHHF rats. Rosuvastatin alone prevented LV dilatation and cardiac inflammation similar to standard HF therapy-treated SHHF, despite being unable to normalize blood pressure (BP) or influence cardiac hypertrophy. However, and importantly, the addition of rosuvastatin to the standard HF therapy further prevented LV dilatation, preserved cardiac function, and normalized inflammation.
These data show that the use of rosuvastatin plus a standard HF therapy results in a significant additional improvement in HF and cardiac remodelling in a rat model of HFpEF. These beneficial effects were independent of BP and plasma lipid changes, and seem to be due, at least in part, to decreased myocardial inflammation.
尽管他汀类药物可能为射血分数保留的心力衰竭(HFpEF)患者提供潜在的治疗途径,但尚无研究评估他汀类药物与标准 HF 治疗联合使用,这更能反映临床实践。为了解决这个问题,我们评估了在患有高血压性心力衰竭(SHHF)的大鼠中,瑞舒伐他汀联合标准 HF 治疗是否能进一步改善心脏结构和功能。
2 个月大的 SHHF 大鼠被随机分为四组:(i)未治疗的 SHHF 大鼠;(ii)瑞舒伐他汀治疗的 SHHF 大鼠;(iii)用喹那普利+托拉塞米+卡维地洛(被认为是标准 HF 治疗)治疗的 SHHF 大鼠;和(iv)用标准 HF 治疗联合瑞舒伐他汀治疗的 SHHF 大鼠。用标准抗高血压 HF 治疗对 SHHF 大鼠进行 17 个月的治疗可减轻左心室(LV)腔扩张、心脏肥大、纤维化和炎症,与未治疗的 SHHF 大鼠相比。与标准 HF 治疗组相比,瑞舒伐他汀单独治疗可预防 LV 扩张和心脏炎症,但不能使血压(BP)正常化或影响心脏肥大。然而,重要的是,将瑞舒伐他汀加入标准 HF 治疗中可进一步预防 LV 扩张,维持心脏功能并使炎症正常化。
这些数据表明,在 HFpEF 的大鼠模型中,使用瑞舒伐他汀加标准 HF 治疗可显著改善 HF 和心脏重塑。这些有益作用独立于 BP 和血浆脂质变化,并且似乎至少部分归因于心肌炎症的减少。