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Microalbuminuria and cardiovascular autonomic dysfunction are independently associated with cardiovascular mortality: evidence for distinct pathways: the Hoorn Study.

ABSTRACT: OBJECTIVE: Microalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality. RESEARCH DESIGN AND METHODS: We studied 490 individuals from a population-based cohort of individuals aged 50-75 years who were followed for a median period of 13.6 years. Microalbuminuria was defined as an albumin-to-creatinine ratio > or =2.0 mg/mmol in an early-morning spot-urine sample. Ten parameters reflecting different aspects of cardiovascular autonomic function were measured and compiled into a total score of C-AD (mean of separate z scores). The association between C-AD and microalbuminuria was estimated by multiple linear regression, and relative risks (RRs) for cardiovascular mortality were estimated by Cox proportional hazards analyses. RESULTS: After adjustments for age, sex, glucose tolerance status, and other risk factors, C-AD was associated with microalbuminuria (beta = 0.16 [95% CI 0.01-0.33]), and both microalbuminuria (RR 2.09 [1.07-4.08]) and C-AD (1.74 [1.04-2.89]) were associated with cardiovascular mortality. These associations did not change after further mutual adjustment for C-AD (2.13 [1.09-4.17]) or microalbuminuria (1.76 [1.05-2.94]), respectively. CONCLUSIONS: Both microalbuminuria and C-AD are independently associated with cardiovascular mortality, and the excess mortality attributable to microalbuminuria cannot be explained by C-AD.

SUBMITTER: Beijers HJ

PROVIDER: S-EPMC2732136 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Microalbuminuria and cardiovascular autonomic dysfunction are independently associated with cardiovascular mortality: evidence for distinct pathways: the Hoorn Study.

Beijers Hanneke J B H HJ Ferreira Isabel I Bravenboer Bert B Dekker Jacqueline M JM Nijpels Giel G Heine Robert J RJ Stehouwer Coen D A CD

Diabetes care 20090629 9

<h4>Objective</h4>Microalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardio ...[more]

PMID: 19564456

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Project description:OBJECTIVE:The primary aim of this secondary analysis was to determine whether cardiac autonomic neuropathy independently predicted adverse cardiac outcomes in asymptomatic individuals with type 2 diabetes. Additional aims include the determination of the correlation of standard autonomic testing measures and power spectral analysis of heart rate variability, and the association of diabetes-related and cardiac risk factors with cardiac autonomic neuropathy measures. METHODS:Cardiac autonomic neuropathy was assessed at the study entry into the Detection of Ischemia in Asymptomatic Diabetics study, using autonomic heart rate and blood pressure testing, and power spectral analysis of heart rate variability. All participants were prospectively followed for the composite clinical outcome of cardiac death, acute coronary syndromes, heart failure, or coronary revascularization. RESULTS:Over 5?years of follow-up, 94 of 1119 (8.4%) subjects developed symptomatic cardiac disease. In unadjusted bivariate analyses, abnormalities in several cardiac autonomic neuropathy tests, including lower Valsalva and Standing Heart Rate Ratios, higher resting Heart Rate, greater systolic blood pressure decrease on standing, and lower low-frequency power, were predictive of symptomatic disease. Independent predictors of poor cardiac outcome were a lower Valsalva Heart Rate Ratio, non-Black ethnicity, longer diabetes duration, higher glycated hemoglobin (HbA1c), insulin use, reported numbness in the extremities, higher pulse pressure, family history of coronary artery disease, and higher waist-to-hip ratio. Clinical factors independently associated with a lower Valsalva Heart Rate Ratio were insulin use, clinical proteinuria, higher pulse pressure, use of angiotensin-converting enzyme inhibitor and non-Black ethnicity. CONCLUSION:Cardiac autonomic neuropathy predicted adverse cardiac outcomes in asymptomatic type 2 diabetes without known cardiac disease. Clinical variables may help to identify patients who might have cardiac autonomic neuropathy and warrant consideration for autonomic testing.

Project description:Background: Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. Objective: This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. Method: A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug*, antipsychotic*, schizophrenia, schizophren*, psychos*, psychotic*, mental ill*, mental disorder*, neuroleptic*, cardiovascular*, cardiovascular diseases, clozapine*, clozaril*, autonomic*, sympathetic*, catecholamine*, norepinephrine, noradrenaline, epinephrine, adrenaline. Results: The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. Conclusion: The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.

Project description:ObjectivesCirculatory dysfunction has been associated with mortality in children with septic shock. However, the mortality risk attributable to myocardial dysfunction per se has not been established, and the association between myocardial dysfunction and mortality is confounded by illness severity. The objective was to determine if sepsis-associated myocardial dysfunction defined by low left ventricular ejection fraction or global longitudinal strain is associated with mortality in pediatric septic shock after adjusting for baseline mortality probability.DesignRetrospective, observational study.SettingSingle-center, quaternary-care PICU.PatientsChildren less than 18 years old admitted to the PICU from 2003 to 2018 who had an echocardiogram performed within 48 hours of septic shock identification and Pediatric Sepsis Biomarker Risk Model II data available.InterventionsNone.Measurements and main resultsAll echocardiograms were reread by a cardiologist blinded to patient data for left ventricular ejection fraction and global longitudinal strain. Low left ventricular ejection fraction was defined as less than 45%, and low global longitudinal strain was defined as greater than z score of -2 for body surface area. Multivariable logistic regression separately analyzed the associations of low left ventricular ejection fraction and low global longitudinal strain with mortality, adjusting for Pediatric Sepsis Biomarker Risk Model II mortality risk. A post hoc logistic regression analyzed the association of left ventricular ejection fraction as a continuous variable with mortality, where linearity was maintained for left ventricular ejection fraction less than 65%. Eighteen percent of 181 children had low left ventricular ejection fraction. After adjusting for baseline mortality risk, low left ventricular ejection fraction remained independently associated with mortality (odds ratio, 4.4 [1.0-19.8]; p = 0.0497). Likewise, left ventricular ejection fraction was associated with mortality (odds ratio, 0.96 [0.93-0.99]; p = 0.037) on multivariable analysis for left ventricular ejection fraction less than 65%. Thirty-six percent of 169 children had low global longitudinal strain, and low global longitudinal strain was also independently associated with mortality (odds ratio, 4.6 [1.2-18.0]; p = 0.027).ConclusionsSepsis-associated myocardial dysfunction, whether defined by low left ventricular ejection fraction or low global longitudinal strain, is an independent risk factor for mortality in pediatric septic shock after accounting for the confounding effects of septic shock severity.

Project description:Introduction: Syncope and orthostatic intolerance in paced patients constitute a common clinical dilemma. We, thus, aimed to determine the etiology of syncope and/or symptoms of orthostatic intolerance in paced patients. Methods: Among 1,705 patients with unexplained syncope and/or orthostatic intolerance that were investigated by cardiovascular autonomic tests, including Valsalva maneuver, active standing, carotid sinus massage, and tilt-testing, 39 patients (2.3%; age 65.6 years; 39% women) had a cardiac implantable electronic device (CIED). We explored past medical history, diagnoses found during cardiovascular autonomic tests, and the further clinical workup, in case of negative initial evaluation. Results: An etiology was identified during cardiovascular autonomic tests in 36 of the 39 patients. Orthostatic hypotension (n = 16; 41%) and vasovagal syncope (n = 12; 31%) were the most common diagnoses. There were no cases of pacemaker dysfunction. The original pacing indications followed guidelines (sick-sinus-syndrome in 16, atrioventricular block in 16, atrial fibrillation with bradycardia in five). Twenty-two of the 39 patients (56%) had experienced syncope prior to the original CIED implantation. Orthostatic hypotension was diagnosed in seven (32%) and vasovagal syncope in nine (41%) of these patients. Of the 17 patients that had not experienced syncope prior to the original CIED implantation, nine patients (53%) were diagnosed with orthostatic hypotension and vasovagal syncope was diagnosed in three (18%). Of the 39 patients, two had implantable cardioverter-defibrillators to treat malignant ventricular arrhythmias diagnosed after syncopal episodes. Conclusion: Cardiovascular autonomic tests reveal the etiology of syncope and/or orthostatic intolerance in the majority of paced patients. The most common diagnosis was orthostatic hypotension (40%) followed by vasovagal syncope (30%), whereas there were no cases of pacemaker dysfunction. Our results emphasize the importance of a complete diagnostic work-up, including cardiovascular autonomic tests, in paced patients that present with syncope and/or orthostatic intolerance.

Dataset Information

Microalbuminuria and cardiovascular autonomic dysfunction are independently associated with cardiovascular mortality: evidence for distinct pathways: the Hoorn Study.

Publications

Microalbuminuria and cardiovascular autonomic dysfunction are independently associated with cardiovascular mortality: evidence for distinct pathways: the Hoorn Study.

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