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      Influenza Vaccination is Associated with Lower Risk of Acute Coronary Syndrome in Elderly Patients with Chronic Kidney Disease

      research-article
      , PhD, , MD, , MD, , MS, , MD, , MD, PhD, , MD, PhD
      Medicine
      Wolters Kluwer Health

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          Abstract

          Elderly patients with chronic kidney disease (CKD) are at a higher risk of hospitalization for cardiovascular diseases (CVD). Previous studies have showed that influenza vaccination could reduce the risk of recurrent major cardiovascular events in patients with CVD. However, the effects of influenza vaccination on the reduction of first hospitalizations for acute coronary syndrome (ACS) in elderly patients with CKD remain unknown.

          We conducted a cohort study using data from the Taiwan Longitudinal Health Insurance Database 1997 to 2008. This cohort study comprised elderly patients (ages ≥55 years) with a recorded diagnosis of CKD (n = 4406) between January 1, 1999, and December 31, 2007. Each patient was followed up until the end of 2008. To minimize the selection bias of vaccine therapy, a propensity score adjustment was applied. The hazard ratio (HR) and 95% confidence interval (CI) for the association between the influenza vaccination and the occurrence of first hospitalization for ACS was evaluated by Cox proportional hazards regression. We further categorized the patients into 4 groups according to their vaccination status (unvaccinated, and total number of vaccinations: 1, 2–3, and ≥4).

          We found that elderly CKD patients without prior CVD history receiving influenza vaccination exhibited a lower risk of hospitalization for ACS (adjusted HR = 0.35, 95% CI 0.30–0.42; P < 0.001). We observed consistent protective effects regardless of age groups (55–64, 65–74, and ≥75), gender, and seasonality of influenza. When the patients were stratified according to the total number of vaccinations, the adjusted HRs for first ACS hospitalization were 0.62 (95% CI 0.52–0.81), 0.35 (95% CI 0.28–0.45), and 0.13 (95% CI 0.09–0.19) for patients who received 1, 2 to 3, and ≥4 vaccinations. There was a significant trend of decreasing risk of ACS hospitalization with an increasing number of vaccinations.

          The results of our observational study could strengthen the annual vaccination policy and physicians should be aware of missed opportunities to vaccinate elderly patients with CKD against influenza. The potential public health impact of influenza vaccination, particularly in the elderly CKD patients without a history of CVD, who are at risk for ACS, should be further explored.

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          Most cited references28

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          Chronic kidney disease: effects on the cardiovascular system.

          Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.
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            Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.

            The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups. The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment. Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction. Copyright 2004 Massachusetts Medical Society
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              Epidemiological features of CKD in Taiwan.

              The incidence of end-stage renal disease (ESRD) in Taiwan is the highest in the world. However, epidemiological features of earlier chronic kidney disease (CKD) have not been investigated. Since implementation of the National Health Insurance Program in 1995, more than 96% of the population in Taiwan has been enrolled. A nationally representative cohort of 200,000 individuals randomly sampled from the National Health Insurance enrollees was followed up from 1996 to 2003. Clinical conditions were defined by using diagnostic codes. The prevalence and incidence of clinically recognized CKD were assessed. We also identified risk factors associated with the development of CKD. The prevalence of clinically recognized CKD increased from 1.99% in 1996 to 9.83% in 2003. The overall incidence rate during 1997 to 2003 was 1.35/100 person-years. The multivariate model indicates that age is a key predictor of CKD, with an odds ratio of 13.95 for the group aged 75-plus years compared with the group younger than 20 years. Other factors associated with increased risk for the development of CKD include diabetes, hypertension, hyperlipidemia, and female sex. The prevalence and incidence of CKD in Taiwan are relatively high compared with other countries. Our finding provides a reasonable explanation for the subsequent epidemic of ESRD in Taiwan. Further study is needed to identify the entire burden of CKD and the effectiveness of risk-factor modification.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                February 2016
                08 February 2016
                : 95
                : 5
                : e2588
                Affiliations
                From the Taipei Cancer Center (C-IC, Y-AF), Cancer Center, Wan Fang Hospital (C-IC, Y-AF), Department of Healthcare Administration (C-IC), Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital (P-FK, J-CL, L-CS), Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital (MYW), College of Medical Science and Technology (JSM), and Department of Internal Medicine, School of Medicine, College of Medicine (P-FK, JCL), Taipei Medical University, Taipei, Taiwan; City of Hope National Medical Center, Duarte, CA (JSM).
                Author notes
                Correspondence: Li-Chin Sung, Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Rd, Zhonghe District, New Taipei City 23561, Taiwan (e-mail: 10204@ 123456s.tmu.edu.tw ).
                Article
                02588
                10.1097/MD.0000000000002588
                4748883
                26844466
                ace2ca22-b718-4c93-a8ed-6b33d4d311b2
                Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

                History
                : 30 May 2015
                : 24 December 2015
                : 28 December 2015
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