Clinical ScienceEffect of Renin–Angiotensin System Inhibition on Cardiovascular Events in Older Hypertensive Patients with Metabolic Syndrome
Introduction
Metabolic syndrome (MetS), a constellation of metabolic risk factors, increases the risk for diabetes and cardiovascular events [1], [2], [3], including cardiovascular disease mortality [4], [5], [6], all-cause mortality [4], [5], [6], and coronary heart disease mortality [6]. The pathogenesis of MetS is complex and incompletely understood, but obesity and insulin resistance contribute to its development [7].
The National Cholesterol Education Program’s (NCEP) Adult Treatment Panel III (ATP) criteria represent the most widely used definition for MetS. MetS, as defined by the ATP III criteria, is estimated to be prevalent in 28% of US adults [8]. The prevalence of MetS increases with age, reaching peak levels in the sixth decade for men and the seventh decade for women [9].
Current pharmacologic management of MetS focuses on the specific risk factors without targeting the underlying insulin resistance [10]. Several lines of evidence suggest that the renin–angiotensin system is both a contributor and target for several risk factors associated with the metabolic syndrome [11]. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) may improve insulin sensitivity [12], [13], [14], decrease the risk of type 2 diabetes [15], improve endothelial function [16], and reduce atherosclerosis and cardiovascular disease risk [17]. Whether ACEI and ARB improve clinical cardiovascular outcomes in hypertensive older patients with MetS is yet to be investigated. The purpose of this study is to evaluate the association between the use of ACEI/ARB and incident cardiovascular events in older adults with hypertension and MetS.
Section snippets
Data Source
We used data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study conducted by the National Heart Lung and Blood Institute (NHLBI) in adults aged 65 and older, to evaluate risk factors for the development and progression of cardiovascular events. The purpose and design of CHS have been published previously [18]. Briefly, the CHS consisted of over 5800 participants randomly selected from Medicare eligibility lists in four U.S. communities in North Carolina,
Results
Of the original 5888 subjects enrolled in the CHS dataset, 1519 subjects had a history of cardiovascular events at baseline (including coronary heart disease, CHF, stroke or TIA). Of the remaining 4369 subjects, 3443 were free from diabetes at baseline. As we were interested in the subjects who used antihypertensive medications, we included in the analysis those who used at least one antihypertensive medication during the study (n = 2412). Out of these individuals, 945 had MetS as defined by ATP
Discussion
MetS is highly prevalent in older individuals [9] and has been associated with future cardiovascular events [1], [2], [3]. ACEIs and ARBs may have beneficial effects on insulin sensitivity [12], [13], [14], the major underlying pathophysiologic feature of MetS. Few studies reported the effect of ACEI/ARB in patients with MetS [28], [29], [30]. These studies were short-term, and the effects of ACEI/ARB on the clinical cardiovascular endpoints were not assessed. Therefore, we sought to determine
Author Contributions
H.H.Z. collected and analyzed data, and drafted the manuscript. K.I.C. designed the study, obtained funding, supervised data collection and analysis, and finalized the manuscript. S.E.H., D.P.M. and P.W.S. contributed to data interpretation and analyses.
Funding
This work was supported in part by National Institutes of Health Grant K23HD049454 (to K.I.C) and Fulbright Scholarship (to H.H.Z.). The Cardiovascular Health Study (CHS) was conducted and supported by the NHLBI in collaboration with the CHS investigators. This manuscript was prepared using a limited access dataset obtained from the NHLBI and does not necessarily reflect the opinions or views of the CHS or the NHLBI.
Conflict of interest
There is no relevant conflict of interest to be disclosed.
Acknowledgments
None.
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