Ressonância Magnética Cardíaca : Correlação entre Biomarcadores e Idade Aging and Cardiac Magnetic Resonance : Correlation between Biomarkers and Age

1Universidade Federal Fluminense – Faculdade de Medicina – Departamento de Radiologia – Niterói, RJ – Brasil 2Centro de Imagem Complexo Hospitalar de Niterói – Niterói, RJ – Brasil 3Universidade Federal do Rio de Janeiro – Faculdade de Medicina – Departamento de Radiologia – Rio de Janeiro, RJ – Brasil 4Clínica ProEcho – Niterói, RJ – Brasil 5Universidade Federal Fluminense – Faculdade de Medicina – Programa de Pós-graduação em Ciências Cardiovasculares (Mestrado) – Niterói, RJ – Brasil


Introduction
The biggest cause of death worldwide is cardiovascular disease, according to the World Health Organization (WHO) 1 .Approximately 17.3 million people died from cardiovascular diseases in 2008, accounting for 30.0% of all deaths worldwide.Of deaths from cardiovascular diseases, 7.3 million were due to coronary artery disease and 6.2 million from stroke 1 .The number of deaths from cardiovascular diseases will reach 23.3 million by 2030, making it, alone, the leading cause of death 2 .
According to the Information Technology Department of the Brazilian Healthcare System (DATASUS) 3 , the highest mortality rate in 2009, in Brazil, was from cardiovascular diseases (31.25%).By analyzing by age group, cardiovascular disease prevails as the main cause of death from the fifth decade of life 3 .Age is the most important risk factor when it comes to the risk of cardiovascular events and development of heart failure.The MESA study (Multi-Ethnic Study of Atherosclerosis) 4 demonstrated in an exemplary manner that non-invasive methods, especially cardiac magnetic resonance imaging (MRI), with different biomarkers, were related to aging and, therefore, could correctly predict cardiovascular events 4 .The use of these noninvasive methods can help prevent and improve the clinical management of asymptomatic individuals, hence avoiding unnecessary public spending.This should be better considered in public policies and in private medicine, currently governed by healthcare plans because the elderly population tend to double in the next decades [4][5][6][7][8] .
Publications addressing the current use of the method and its relationship with population aging will help understanding the correct applicability of the method.This will make MRI as a diagnostic tool for the management of cardiovascular diseases.The objective of this study is to describe the clinical and imaging indicators that best correlate with aging in a sample population and in a low-risk group who underwent MRI.

Methods
This is a descriptive and retrospective study that analyzed MRI tests conducted from May 2007 to April 2011, totaling 1,000 tests in two private institutions in the city of Niterói, RJ: Complexo Hospitalar de Niterói (CHN) and Clínica ProEcho de Niterói (PE).
This study has been approved by the Research Ethics Commission of the HUCFF/FM/UFRJ under no.046/11-CEP.
To analyze the clinical and imaging indicators that best correlated with aging, sample population and a group with low risk for CAD and heart failure were considered and selected for having a body mass index <30 kg/m 2 , systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg, normal left ventricular ejection fraction (LVEF) (50-70%), absence of delayed enhancement on MRI and no clinical complaints.

MRI Protocol
The testing routine in both institutions follows identical protocols.
At CHN, the tests were performed on 1.5 Tesla equipment, Magnetom Symphony® (Siemens Medical Solutions, Erlangen, Germany), with four-element phasedarray cardiac coil and cardiac gating.
At PE, the tests were performed on 1.5 Tesla equipment, SIGNA GE Horizon® (General Electric, Milwaukee, USA), with high performance gradients (32 mT amplitude and slew rate 150 T/m/s), four-element phased-array cardiac coil and cardiac gating.On all the tests, paramagnetic contrast was used.At PE, gadoversetamide (Optimark®, Mallinckrodt, USA) was used and at CHN, gadodiamide (Omniscan®, GE Healthcare, USA) was used.The contrast medium dose was 0.2 mL/kg injected through infusion pump at a rate of 5 mL/s.
All images were stored in DICOM (Digital Imaging and Communications in Medicine) and transferred to off-theshelf workstations (ADW 4.3, GE Medical Systems and Leonardo, Siemens Medical Solutions).MRI evaluated the diameters of the great vessels, left ventricular systolic and diastolic diameters, ejection fraction and right ventricular and left atrial lengths.All tests were analyzed by two specialists independently.Conflicting results were resolved by consensus.

Statistical Analysis
The continuous variables were expressed as mean±standard deviation and categorical variables were expressed in frequencies according to the situation.Analysis was performed by linear and multivariate regression to evaluate the aging population with clinical or imaging markers.STATA ® , version 12.0 (Stata Corp LP College Station, Texas, USA; and Excel plug-in (Daniel's XL Toolbox, version 4.01, Boston, MA, USA) was used for statistical analysis and significance level <0.05 was considered.

Results
The average time for completing the MRI tests was approximately 42.3±9.6minutes.
Table 1 shows the distribution of patients submitted to MRI by age group and Table 2 describes the main indications of these tests.4).
As for the image indicators, all diameters of the great vessels were significantly correlated with aging (p<0.001).This was also identified for the greater length of the right ventricle (RV) and the anteroposterior diameter of the left atrium (p<0.001).However, the analysis of the low-risk group or group with no abnormal findings on imaging studies, the only markers with significant correlation with age were the ascending aortic diameter (r=0.52,p<0.001) and greater RV length (r=-0.31,p=0.03).The latter marker is always inversely significant.Table 4 describes the correlations between clinical and imaging markers using age as an independent variable.

Discussion
This study evaluated 1 000 MRI tests performed by clinical routine indication in the city of Niterói, RJ, and demonstrated that the method is being carried out on a daily basis, aided by assistant physicians both at the outpatient care and in the emergency room (in-hospital).It also found that MRI is being used for all age groups and among the various indications, investigation of myocardial ischemia under pharmacological stress and evaluation of patients with suspected myocarditis are the indications that most help the assistant physicians in that region, in their routine practice.
By assessing the main indications and comparing them against the Brazilian guideline, all of them are among classes I and IIa: investigation of myocardial ischemia (IIa), investigation of myocardial viability (I), assessment of myocarditis (IIa) and Arrhythmogenic Right Ventricular Dysplasia (ARVD) (I), among others, demonstrating that the method is being properly used on a daily basis.
It was observed in this study that in the sample population or in the low-risk group, the quantification of the ascending aorta diameter is the marker that best correlates with the population aging and which can probably be used for risk characterization and stratification in both situations.
Anatomical and physiological abnormalities of aging in the cardiovascular system affect cardiac function.
Structural changes lead to decreased functional reserve, limiting performance in higher demand situations 8 .With aging, there is reduced arterial compliance with increased peripheral resistance and consequent increase in systolic blood pressure that ultimately results in increased afterload, making ventricular ejection difficult 9,10 .In this study, we observed that systolic blood pressure is a strong marker of aging and should be the focus of constant clinical observation for reducing cardiovascular risk or developing heart failure in the elderly population 11 .
It is true that the infiltration of fat cells in specialized muscle cells of the conduction system and replacement of the latter for collagen and elastic fibers of the connective tissue occurs over time, slowly but continuously, starting around the age of 60 4 .Heart rate gradually decreases and does not adequately address the most demanding situations 10 .This study was also able to demonstrate such situation, since there is an inverse relationship between heart rate and sample population aging in the low-risk group.
In the sample population of this study, clinical data such as weight and systolic blood pressure were the markers that best correlated with aging.However, these data cannot be used for a low-risk population.
As widely studied, population aging will increase the number of patients with heart failure, and this may be one of the great situations of spending on public health in the near future.The incidence of heart failure continues to grow even with the advance of techniques for better assessment and treatment.A strategy to change this situation is to develop tools to identify individuals at increased risk for heart failure, allowing therapies to prevent or delay its onset 5,12,13 .In addition to stratifying the population with biomarkers [14][15][16] or echocardiogram 17 , scores with multiple risk markers based on clinical data have been used for this purpose.
The Health Aging and Body Composition Heart Failure score 18 has been recently developed and validated in a multiethnic elderly population grouped in the Health ABC study to prevent the risk of acute heart failure in five years and was considered higher than the Framingham heart failure risk score.Not only clinical markers, but imaging markers, have been evaluated.A study 19 that added the Health Aging and Body Composition Heart Failure score with cardiac structural and functional abnormalities to create heart failure predictors in five years in a younger population found left ventricular (LV) dysfunction and LV hypertrophy as the two most parameters most associated with this risk.
In this study, the diameter of the large vessels was correlated with aging (p<0.001).The same was found for the greater length of the RV and the anteroposterior diameter of the left atrium (p<0.001).In the group without risk factors for coronary artery disease, the only indicators correlated with increasing age were the ascending aortic diameter (r=0.52,p<0.001) and greater RV length (r=-0.31,p=0.03).Aorta diameter, primarily in the ascending portion, increases with age, being a known indicator of aging [20][21][22] .Bingham and Hachamovitch 22 showed enlarged left atrium related to aging.This abnormality directly influences LV volume and mass, the latter being a marker of diastolic function.
Several limitations are present in this study, mainly due to the retrospective design and lack of information necessary to determine cardiovascular risk.However, it is considered that this may be an important factor in some clinical situations in everyday life, not undermining the merit of this information.

Conclusion
Several biomarkers of MRI can be used for aging assessment, but among those presented in this paper, the diameter of the aorta and the right ventricle were the ones that best correlated for the sample population and for the low cardiovascular risk group.

Potential Conflicts of Interest
This study has no relevant conflicts of interest.

Table 1 Distribution of patients who underwent MRI by age and sex
MRI -magnetic resonance imaging

Table 3 Demographic and clinical data of the MRI population Demographic and clinical data
Data expressed as mean±standard deviation MRI -magnetic resonance imaging; RV -right ventricle; LA -left atrium; LVEF -left ventricular ejection fraction

Table 4 Correlation between clinical imaging data with age (aging)
Note: *p-value refers to multivariate analysis, relating age as the dependent variable.**The analysis was performed looking for a model with no comorbidities.It considered the absence of delayed enhancement Fernanda Boldrini Assunção receives a Research Incentive Grant from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Vítor Frauches Souza and Wilter dos Santos Ker receive a Masters' Grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).Association This manuscript is part of the Master's Dissertation of Adriana Dias Barranhas from the Radiology Graduate Program of Universidade Federal Rio de Janeiro, together with the Cardiovascular Sciences Graduate Program of Universidade Federal Fluminense.