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      Excess Risk for Atherosclerotic Cardiovascular Outcomes Among US Adults With HIV in the Current Era

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          Abstract

          Background

          In the 2000s, adults with HIV had a higher risk for atherosclerotic cardiovascular disease ( ASCVD) compared with those without HIV. There is uncertainty if this excess risk still exists in the United States given changes in antiretroviral therapies and increased statin use.

          Methods and Results

          We compared the risk for ASCVD events between US adults aged ≥19 years with and without HIV who had commercial or supplemental Medicare health insurance between January 1, 2011, and December 31, 2016. Beneficiaries with HIV (n=82 426) were frequency matched 1:4 on age, sex, and calendar year to those without HIV (n=329 704). Beneficiaries with and without HIV were followed up through December 31, 2016, for ASCVD events, including myocardial infarction, stroke, and lower extremity artery disease hospitalizations. Most beneficiaries were aged <55 years (79%) and men (84%). Over a median follow‐up of 1.6 years (maximum, 6 years), there were 3287 ASCVD events, 2190 myocardial infarctions, 891 strokes, and 322 lower extremity artery disease events. The rate per 1000 person‐years among beneficiaries with and without HIV was 5.53 and 3.49 for ASCVD, respectively, 3.58 and 2.34 for myocardial infarction, respectively, 1.49 and 0.94 for stroke, respectively, and 0.65 and 0.31 for lower extremity artery disease hospitalizations, respectively. The multivariable‐adjusted hazard ratio (95% CI) for ASCVD, myocardial infarction, stroke, and lower extremity artery disease hospitalizations comparing beneficiaries with versus without HIV was 1.29 (1.18–1.40), 1.26 (1.13–1.39), 1.30 (1.11–1.52), and 1.46 (1.11–1.92), respectively.

          Conclusions

          Adults with HIV in the United States continue to have a higher ASCVD risk compared with their counterparts without HIV.

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          Most cited references28

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          Characteristics, Prevention, and Management of Cardiovascular Disease in People Living With HIV: A Scientific Statement From the American Heart Association

          As early and effective antiretroviral therapy has become more widespread, HIV has transitioned from a progressive, fatal disease to a chronic, manageable disease marked by elevated risk of chronic comorbid diseases, including cardiovascular diseases (CVDs). Rates of myocardial infarction, heart failure, stroke, and other CVD manifestations, including pulmonary hypertension and sudden cardiac death, are significantly higher for people living with HIV than for uninfected control subjects, even in the setting of HIV viral suppression with effective antiretroviral therapy. These elevated risks generally persist after demographic and clinical risk factors are accounted for and may be partly attributed to chronic inflammation and immune dysregulation. Data on long-term CVD outcomes in HIV are limited by the relatively recent epidemiological transition of HIV to a chronic disease. Therefore, our understanding of CVD pathogenesis, prevention, and treatment in HIV relies on large observational studies, randomized controlled trials of HIV therapies that are underpowered to detect CVD end points, and small interventional studies examining surrogate CVD end points. The purpose of this document is to provide a thorough review of the existing evidence on HIV-associated CVD, in particular atherosclerotic CVD (including myocardial infarction and stroke) and heart failure, as well as pragmatic recommendations on how to approach CVD prevention and treatment in HIV in the absence of large-scale randomized controlled trial data. This statement is intended for clinicians caring for people with HIV, individuals living with HIV, and clinical and translational researchers interested in HIV-associated CVD.
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            Narrowing the Gap in Life Expectancy Between HIV-Infected and HIV-Uninfected Individuals With Access to Care.

            It is unknown if a survival gap remains between HIV-infected and HIV-uninfected individuals with access to care.
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              Severity of Cardiovascular Disease Outcomes Among Patients With HIV Is Related to Markers of Inflammation and Coagulation

              Background In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein (hsCRP), and D‐dimer; HIV‐induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Methods and Results Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL‐6, D‐dimer, hsCRP, and a 1‐unit increase in an IL‐6 and D‐dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow‐up. Hazard ratios (95% CI) for all‐cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL‐6, D‐dimer, hsCRP, and the IL‐6 and D‐dimer score. Conclusions Higher IL‐6 and D‐dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD event. Clinical Trial Registration URL: http://www.clinicaltrial.gov Unique identifier: SMART: NCT00027352, ESPRIT: NCT00004978, SILCAAT: NCT00013611.
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                Author and article information

                Contributors
                robert.rosenson@mssm.edu
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                27 December 2019
                07 January 2020
                : 9
                : 1 ( doiID: 10.1002/jah3.v9.1 )
                : e013744
                Affiliations
                [ 1 ] Icahn School of Medicine at Mount Sinai New York NY
                [ 2 ] University of Alabama at Birmingham Birmingham AL
                [ 3 ] Amgen, Inc Thousand Oaks CA
                Author notes
                [*] [* ] Correspondence to: Robert S. Rosenson, MD, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY 10029‐6574. E‐mail: robert.rosenson@ 123456mssm.edu
                Article
                JAH34670
                10.1161/JAHA.119.013744
                6988153
                31880980
                7610ee4c-a4cc-4fcd-afba-49148c0fc708
                © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 02 August 2019
                : 07 November 2019
                Page count
                Figures: 2, Tables: 3, Pages: 11, Words: 7446
                Funding
                Funded by: Amgen, Inc
                Categories
                Original Research
                Original Research
                Epidemiology
                Custom metadata
                2.0
                07 January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.4 mode:remove_FC converted:06.01.2020

                Cardiovascular Medicine
                hiv,myocardial infarction,peripheral artery disease,stroke,cardiovascular disease,epidemiology,risk factors,primary prevention

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