Vascular Protection of Dual Therapy (Atorvastatin-Amlodipine) in Hypertensive Patients

Abstract

Hypertension frequently coexists with other cardiovascular risk factors, such as hypercholesterolemia, and their combination is associated with a greater rate of cardiovascular events. Recent clinical data support that treatment of hypertensive patients with a combination of antihypertensive and lipid-lowering therapies leads to a higher reduction in the incidence of cardiovascular events. In the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), an optimal prevention of cardiovascular events was reached in patients who were randomly assigned to atorvastatin and the amlodipine treatment. However, the potential underlying mechanisms of these vascular protective effects are not fully elucidated. Because experimental studies have shown that statins and calcium channel blockers have antiatherosclerotic effects, the effect of atorvastatin alone or in combination with amlodipine was analyzed in the protein secretion profile of atherosclerotic plaques that were cultured ex vivo. In this respect, the addition of atorvastatin and amlodipine to atherosclerotic plaques normalized the levels of the different released proteins to that obtained from healthy arteries. This review highlights recent clinical and experimental studies that support that a combined treatment of hypertensive patients with both statins and calcium channel blockers could promote a higher reduction in their global cardiovascular risk profile and associated mortality. As an example, the application of a proteomic approach to assess the modulation by atorvastatin alone or in combination with amlodipine on the proteins that are released by atherosclerotic plaques has allowed the identification of novel therapeutic targets by which these drugs could promote their additive/synergic effects.J Am Soc Nephrol 17: S189 -S193, 2006. doi: 10.1681/ASN.2006080913 N ephrologists traditionally have been involved in the care of patients with hypertension, because this disorder is both cause and consequence of kidney disease. However, hypertension frequently coexists with other cardiovascular risk factors, such as hypercholesterolemia, and their combination is associated with a greater rate of cardiovascular events (1). Clinical and experimental studies that were performed in the past few years suggested that when treating hypertensive patients, all of these factors should be considered to achieve a higher reduction in cardiovascular morbidity and mortality on these patients. Combined Antihypertensive and LipidLowering Therapies in the Clinical PracticeA large number of clinical trials have demonstrated that treatment of either hypercholesterolemia or hypertension leads to a reduction in the incidence of cardiovascular events. Moreover, subgroup analyses that were performed in the Heart Outcomes Prevention Evaluation (HOPE) study showed the benefits of angiotensin-converting enzyme inhibitors in patients who received concomitant statin therapy (2). Similarly, in the Heart Protection Study (HPS), simvastatin diminished cardiovascular even...

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

“…Longer-term studies utilizing combined statin and angiotensin receptor blockers in T2D are required. In patients with hypercholesterolemia and hypertension, evidence supports the anti-atherosclerotic effects of combined statin and calcium channel blocker therapy, particularly the combination of amlodipine and atorvastatin [226,[228][229][230]. Combination therapy with antioxidants.…”

“…Abbreviations: FMD -flow-mediated dilation of the brachial artery, ACh -acetylchollilne, FABF -forearm blood flow, ns -no significant effect, SNP -sodium nitroprusside, BK -bradykinin, L-NMMA -L-nitro-mono-methyl arginine, EPA -eicosapentenoic acid, DHA -docosahexenoic acid, T2D -type 2 diabetes mellitus, AIx -augmentation index, IMT -intima-media thickness, MRI -magnetic resonance imaging, MUFA -monounsaturated fatty acids, omega-3 FA -omega-3 fatty acids, CoQ 10 -coenzyme Q 10 , VCAM-I -vascular cell adhesion molecules 1, RH -reactive hyperemia. References [109,139,143,209,220,221,226,235,241].…”

“…Statins and antihypertensive agents have differing mechanisms of action on the arterial wall. Therefore, it is possible that in combination they will have an additive and synergistic effect on vascular function [109,[225][226][227]. Compared to monotherapy, ramipril combined with simvastatin significantly improved FMD and reduced malondialdehyde (MDA) and hs-CRP levels in hypercholesterolemic T2D patients [225].…”

20 Years of Hypertension Research using Genetically Modified Animals: No Clinically Promising Approaches in Sight

“…calcium channel blockers (escames et al, 2004;Martin-Ventura et al, 2006), the introduction of a "single pill" was suggested Blank et al, 2007).…”

Vascular proteomics

“…However, the potential underlying mechanisms of such vascular protective effects are unknown. Taking into account that statins and calcium channel blockers have antiatherosclerotic effects, we have studied the effect of atorvastatine alone or combined with amlodipine in the protein secretion profile of atherosclerotic plaques (incubated ex vivo) by following the same proteomic approach that we previously described to characterize the atherosclerotic process [39]. From an average of 620 spots detected per gel, 217 protein spots were present at higher levels in the conditioned media of atherosclerotic plaques than in those of the control region, whereas 43 protein spots were decreased or remained unchanged.…”