Abstract
AimsHypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and activating the renin-angiotensin aldosterone system (RAAS) and mevalonate pathways. This review examines how the severity and duration of these risk factors may influence the cardiovascular risk through a reciprocal interplay leading to oxidative stress and pro-inflammatory response. Data synthesisThe review highlights the clinical evidence supporting the benefits of statins and angiotensin-converting enzyme (ACE) inhibitors for hypertension, lipid disorders and ASCVD management, both individually and combined, at all stages of the cardiovascular continuum. ConclusionDrug strategies incorporating an ACE-inhibitor and a statin, and in particular perindopril and atorvastatin, have consistently demonstrated reductions in the rate of ASCVD events in patients with hypertension and lipid disorders, cementing their position as first-line therapies for the management of atherosclerosis complications.
Highlights
Atherosclerotic cardiovascular disease (ASCVD) continues to represent the leading cause of mortality in the world, with 2019 World Health Organization estimates indicating that it was responsible for 16% (8.9 million) of total deaths [1]
The proliferation and migration of monocytes/macrophages and endothelial and smooth muscle cells leading to the progression of atherosclerotic lesions depends on the activity of the matrix metalloproteinases (MMPs), which are regulated by proinflammatory cytokines such as IL-1, TNF-a, and CD40L, all of which are reduced by statins [23,24]
A large observational study in ST-segment elevation myocardial infarction (STEMI) patients that compared patients treated with statin þ angiotensin-converting enzyme (ACE) inhibitor (n Z 8705) and statin þ ARB (n Z 3001) demonstrated that the rates of major adverse cardiovascular events (MACE), MI, and revascularization were similar between the two groups, while a statin/ACE inhibitor combination was associated with a significantly reduced mortality rate [111]
Summary
Atherosclerotic cardiovascular disease (ASCVD) continues to represent the leading cause of mortality in the world, with 2019 World Health Organization estimates indicating that it was responsible for 16% (8.9 million) of total deaths [1]. Disease dataset indicates that the global prevalence of ASCVD is continuing to rise, and the current prevalence rate of 1655 per 100,000 population is expected to exceed 1845 by the year 2030 [2] This trend is driven by population aging, and the increased prevalence of obesity, diabetes, and metabolic syndrome as well as some emerging risk factors such as elevated serum uric acid [3]. The endothelium is a major regulator of vascular homeostasis, but when chronically activated, for example, under conditions of hypertension and hypercholesterolemia, a cascade of inflammatory mechanisms is initiated that potentiate the pro-atherogenic environment and continued atherosclerotic plaque progression [4] This article reviews the evidence on the synergistic effects of statins and ACE inhibitors in atherosclerosis and highlights clinical evidence supporting the benefits of statin and ACE inhibitor combinations for ASCVD management
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