Statins, the renin–angiotensin–aldosterone system and hypertension – a tale of another beneficial effect of statins

Abstract

Background: Statins, a class of lipid lowering drugs, decrease mortality associated with cardiovascular events. As hypercholesterolemia is often accompanied by hypertension, a large number of patients receive therapy with statins and antihypertensive drugs which act via the renin-angiotensin-aldosterone system (RAAS). New guidelines published by the American Heart Association and American College of Cardiology on the treatment of dyslipidaemia and the reduction of atherosclerotic cardiovascular risk, which use a risk prediction algorithm based on risk factors such as hypertension but not low-density lipoprotein (LDL) level, may even further increase the number of patients receiving such concomitant therapy. Method: In this paper we review studies on an interaction between statins, the RAAS and antihypertensive drugs acting via the RAAS. Result: Accumulating evidence suggests that the combination of statins and drugs affecting the RAAS exerts a synergistic effect on the circulatory system. For example, statins may lower arterial blood pressure and augment the effect of antihypertensive drugs acting via the RAAS. Statins may interact with the RAAS in a number of ways i.e. to decrease the expression of receptors for angiotensin II (Ang II), inhibit the Ang II-dependent intracellular signalling, reduce the RAASdependent oxidative stress and inflammation as well as inhibit the synthesis of Ang II and aldosterone. Conclusion:Although statins given either alone or together with antihypertensive drugs acting via the RAAS may lower arterial blood pressure, further research is needed to evaluate the mechanisms and their therapeutic significance.

Asymmetric Dimethylarginine Limits the Efficacy of Simvastatin Activating Endothelial Nitric Oxide Synthase

“…At cellular and molecular levels, simvastatin increases endothelial nitric oxide (eNOS) activity and leads to NO production in endothelial cells (ECs) by regulating a kinase‐dependent pathway and protein‐protein interaction 6, 7. Despite many achievements of statins in treating cardiovascular complications,3, 8, 9, 10 such treatment is not always effective in improving EC function and inflammation, with unclear mechanisms under some circumstances 11, 12. Recently, asymmetric dimethylarginine (ADMA) has been implicated as a contributing factor to the lack of protective effect of statins 13, 14…”

Modifying Effect of Statins on Fatal Outcomes in Chronic Kidney Disease Patients in the Systolic Blood Pressure Intervention Trial: A Post Hoc Analysis

“…Ferrier et al [20] additionally showed that the use of statin in patients with isolated systolic hypertension significantly improved systemic arterial compliance (0.43 ± 0.05 vs. 0.36 ± 0.03 mL/mm Hg, p = 0.03) measured noninva- All-cause mortality and cardiovascular mortality outcomes by subgroup sively by carotid applanation tonometry and Doppler velocimetry of the ascending aorta. This synergistic effect stemming from the combination of antihypertensive therapy and statins appears to transcend cholesterol reduction uniquely and suggests a more intricate form of statin-mediated vascular pleiotropic effect [21,22]. As previously mentioned, lipid-lowering therapy is an important cornerstone in the management of all patients with CKD not on dialysis.…”

Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production

“…For example, statins decrease not only serum cholesterol but also triglyceride levels; in addition, data in the literature suggest that statins can reduce blood pressure while also improving dyslipidemia (e.g., Myerson et al 2005 and reviewed in Drapala et al 2014). Several lines of evidence support the idea that statins can regulate various components of the renin-angiotensin II-aldosterone system (e.g., Long et al 2015and reviewed in Chiong & Miller 2002, Drapala et al 2014.…”

“…For example, statins decrease not only serum cholesterol but also triglyceride levels; in addition, data in the literature suggest that statins can reduce blood pressure while also improving dyslipidemia (e.g., Myerson et al 2005 and reviewed in Drapala et al 2014). Several lines of evidence support the idea that statins can regulate various components of the renin-angiotensin II-aldosterone system (e.g., Long et al 2015and reviewed in Chiong & Miller 2002, Drapala et al 2014. Indeed, a recent well-controlled study demonstrated that statin use in hypertensive and diabetic subjects with statins, in particular lipophilic statins, reduces basal serum aldosterone levels as well as the aldosterone response to angiotensin II and lowsodium diet (Baudrand et al 2015).…”