Migraine and vascular disease biomarkers: A population-based case-control study.

Background The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population. Methods Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30-60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared between groups, also stratifying by sex. Results Fibrinogen and hs-CRP were elevated in migraineurs compared to controls. In logistic regression analyses, MO and MA had increased likelihood of elevated fibrinogen, and MA had increased likelihood of elevated Factor II and hs-CRP. Fibrinogen and Factor II were associated with MA in women but not men. In the migraine subgroup, the total number of years of aura, but not headache, predicted elevated hs-CRP, and the average number of aura, but not headache, attacks predicted all biomarkers but Factor II. Conclusions Elevated vascular biomarkers were associated with migraine, particularly MA, as well as with years of aura and number of aura attacks

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

Aims/hypothesis: We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes. Methods: A cohort of 1066 Scottish men and women aged 60–74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml−1 min−1 (1.73 m)−2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models. Results: A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286). Conclusions/interpretation: Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention

Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary Disease: A Large Case-Controlled Study.

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid-femoral (aortic) pulse wave velocity, augmentation index, and carotid intima-media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima-media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease

Clinical implications of cerebral age-related white matter cerebral changes

Tese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2013Cerebral age-related white matter changes (WMC) designate the changes of the radiological appearance of cerebral white matter, detected either in CT scan or in MRI, of probable vascular aetiology, that are frequently described in elderly people (1,2,3). The clinical significance of those changes has gained attention in the last three decades and remains a controversial issue. Some demographic and vascular risk factors are associated with higher risk of developing more severe WMC, and among these, mainly aging, hypertension and stroke (2, 3, 4). WMC are more frequent in demented patients (5). White matter changes have been implicated in cognitive decline, gait disturbances, urinary dysfunction, personality changes and depression (6), however contradictory results inhibit the consensus in this topic (7). Several questions remained unanswered when we started our study, namely concerning long term cognitive implications of WMC in subjects living in full autonomy. Furthermore, no convincing data was available regarding information on the risk of evolution for any type of dementia taking into account the global spectrum of risk factors. The objectives of this thesis were 1. to study the influence of WMC and vascular risk factors on the neuropsychological performance and on the progression for dementia of non-disabled independent elderly people with WMC; 2. to study the implications of self-perceived memory complaints; 3. to study the meaning of late onset depressive symptoms; and, 4. to clarify if regular physical activity reduces the risk of dementia in elderly subjects with WMC. Our study was conducted within a large European multicentre collaboration (the LADIS study: 11 European centres: Amsterdam, Copenhagen, Florence – coordinator centre-, Graz, Göteborg, Lisbon, Helsinki, Huddinge, Mannheim, Newcastle-upon-Tyne and Paris), that was designed to assess the role of WMC as an independent predictor of the transition from an autonomous functional status to disability in elderly subjects and the role of WMC progression in this transition (8). The Lisbon center took responsibility of all cognitive evaluation and definition of criteria and monitorization of cognitive diagnosis. Inclusion criteria for the study were: (i) 65–84 years of age; (ii) changes in WMC on MRI of any degree, according to the scale of Fazekas (9); and (iii) no disability, as determined by the Instrumental Activities of Daily Living scale (IADL) (10). Patients were referred for the study with minor complaints, incidental findings on cranial imaging caused by non-specific events without impact on daily living activities or were otherwise volunteers (8). Subjects were evaluated at baseline and yearly during 3 years with a comprehensive protocol including registry of demographic and vascular risk factors, co-morbidities, evaluation of depression, quality of life and a neuropsychological battery. Clinical evaluation included the classification of cognitive impairment according to usual clinical criteria (11). MRI was performed at baseline and at 3-year follow-up. The inclusion of subjects started in July 2001, 639 patients were enrolled (mean age 74.1 years-old, SD 5.0, 55% women, 9.6 years of educational level, SD 3.8). From the initial sample, 89% (568), 78.4% (501), and 75% (480) of the patients were followed up in a clinical visit at months 12, 24 and 36. After a median follow-up period of 2.9 years, information on the transition from full autonomy into disability was available for 633 (99%) patients. Forty-three subjects died (6.7% of study sample) until the third year of follow-up. Fifty-one patients missed the complete cognitive evaluation in any of the follow-up clinical visits. For those 51 patients no cognitive diagnosis was attributed, although vital status and IADL were known in those patients. Considering the cognitive diagnosis performed in the last clinical visit, dementia was diagnosed in 90 patients (Vascular dementia, 54; Alzheimer disease, 22; Alzheimer disease with vascular component, 12; Frontotemporal dementia, 2), and 147 patients had cognitive impairment not dementia (Vascular cognitive impairment non dementia - CIND, 86; mild cognitive impairment - MCI, 61). Our study showed that: 1. The severity of WMC is related with worse performance on global measures of cognition, executive functions, speed/motor control, and tests of attention, naming and visuoconstructional praxis in elderly subjects living independently. The impact of WMC on neuropsychological performance was present even when controlling for demographic variables (age and education), vascular risk factors and temporal lobe atrophy. 2. WMC severity is a predictor of cognitive impairment (dementia and not dementia) in elderly subjects with WMC, overtime. WMC and stroke predicted vascular dementia but not Alzheimer’s dementia, while medial temporal atrophy predicted both Alzheimer’s dementia and vascular dementia. Vascular risk factors (diabetes, hypertension and previous stroke) emerged as relevant factors with influence on neuropsychological tests in older people living with full autonomy, independently of WMC severity. After 3 years, diabetes at baseline was the only vascular risk factor that predicted cognitive impairment of any type (dementia and not dementia). 3. Memory complaints are a strong predictor of Alzheimer’s disease and Alzheimer’s disease with vascular component during the follow-up, independently of depressive symptoms and global cognition status at baseline in older subjects with WMC. To the best of our knowledge this is the first study that approaches implications of memory complaints in independent elderlies with white matter changes. Prediction Our study has some limitations, mainly related with a sample selection that was not drawn from the community. Participants were selected in outpatient clinics due to the presence of white matter changes. Patients could have minor complaints or could otherwise be volunteers. So we must be cautious in the generalization of our results. The other main limitation is associated with technological evolution, as the study was designed 10 years ago. However, this study was conducted in the a large heterogeneous population, rigorously assessed with a systematic and comprehensive evaluation, and this sample probably represents the first moment when non-disabled elderly subjects with cerebral white matter changes seek medical attention, and this fact is meaningful for clinical practice. Moreover, despite some missing information in the cognitive evaluation overtime, 99% of the initial sample had information on follow-up data, and follow-up was long enough to have conversion for cognitive impairment and dementia. Moreover, a substantial part of the initial sample was able to repeat MRI.After our work, we think that there is sufficient evidence to sustain that WMC are not an innocuous finding associated with ageing. In clinical practice, we deal frequently with elderly subjects that require an appointment due to the detection of cerebral white matter changes. Our data support the fact that WMC are implicated in the evolution for disability and for cognitive impairment. Furthermore, we identified several risk factors that are implicated in the progression for cognitive impairment, such as diabetes and stroke that appear as potential factors for intervention when preventing dementia. Our results emphasize the key role of both vascular risk factor control and physical activity in reducing the risk of cognitive impairment with ageing. Unfortunately, insufficient information exists concerning the recommendations for the control of the risk factors identified in the elderly in order to prevent dementia. Similarly, there is no recommendation regarding type and intensity of physical activity, influence of other leisure activities and type of intervention in subjects with depressive symptoms in order to be effective when preventing cognitive impairment in subjects with WMC. On the other hand there are still no known drugs specifically designed (or being currently in development) for the prevention of cognitive impairment in small vessel disease, other than those that aim to treat vascular risk factors. One of the clear areas of increasing interest is the impact of diet, risk factors control and physical and leisure activities on cognitive functioning in subjects with white matter changes. These relationships have to be determined by means of interventional studies that should be controlled by imagiological vascular biomarkers. These biomarkers must include sensitive tools for the measure of cerebral WMC as a hallmark of small vessel disease, including novel MRI sequences (diffusion, perfusion and spectroscopy) that allow the visualization of tissue changes in areas of white matter that appear normal using conventional MRI. Additionally, other biomarkers must be taken into account, namely other manifestations of small vessel disease (such as mibrobleeds and lacunes) and atrophy (either regional, including medial temporal lobe atrophy, or global) as potential confounders. Numbers of included subjects must be large enough to allow the control of multiple concomitant factors that can confound the interpretation of results and interfere with the statistical power. Clearly such a study can only be possible in a multicentric setting. Although designing a clinical trial is always limited to the knowledge available at a given time, we are convinced that: 1. any project aiming to study factors that influence cognitive changes in elderly should be controlled for white matter changes; 2. most available sensitive methods for detecting WMC should be used; 3. WMC severity is a potential end-point in cognitive trials.As alterações da substância branca cerebral associadas à idade (ASBC) designam as alterações radiológicas da substância branca cerebral detectadas quer por tomografia axial computadorizada como por ressonância magnética, de etiologia vascular provável, que são frequentemente descritos nas pessoas idosas (1,2,3). O significado clínico destas alterações tem sido objecto de investigação nas últimas três décadas e continua um assunto controverso. Alguns factores demográficos e factores de risco vascular associam-se a maior risco de ASBC mais severas, e entre aqueles, sobretudo a idade, a hipertensão e o acidente vascular cerebral (2, 3, 4). As ASBC são mais frequentes em doentes com demência (5). As ASBC têm sido implicadas no declínio cognitivo, em alterações da marcha, na disfunção urinária e em alterações da personalidade e depressão (6), no entanto, os resultados contraditórios dos diversos estudos têm impedido um consenso neste campo (7). Várias questões permaneciam em aberto quando iniciámos o estudo, especialmente a questão de saber se as ASBC poderiam implicar deterioração cognitiva a longo termo, em indivíduos completamente independentes com algum grau de ASBC. Adicionalmente, não existia nenhum dado que evidenciasse algum risco de evolução para algum sub-tipo de demência, tendo em consideração o espectro global dos factores de risco concomitantes. Os objectivos deste trabalho foram 1) investigar a influência das ASBC e dos factores de risco vasculares no desempenho neuropsicológico e na progressão para demência em indivíduos idosos com alterações das ASBC, independentes nas actividades de vida diária; 2) investigar as implicações das queixas de memória nos mesmo indivíduos; 3) investigar o significado dos sintomas depressivos de início tardio; e, 4) esclarecer se a actividade física regular reduz o risco de demência em indivíduos idosos com ASBC. Este trabalho foi levado a cabo integrado num estudo cooperativo multicêntrico Europeu (o estudo LADIS: 11 centros europeus: Amsterdão, Copenhaga, Florença –centro coordenador-, Graz, Gotemburgo, Lisboa, Helsínquia, Huddinge, Mannheim, Newcastle-upon-Tyne e Paris), que foi desenhado para avaliar o papel das ASBC como factor preditor independente da transição de um estado de completa autonomia funcional para incapacidade no idoso, e ainda o papel da progressão das ASBC nesta transição (8). O centro de Lisboa teve a responsabilidade de definir a avaliação cognitiva, os critérios cognitivos e ainda a monitorização dos diagnósticos cognitivos ao longo do estudo. Os critérios de inclusão do estudo foram: (i) 65–84 anos; (ii) ASCB de qualquer gravidade (de acordo com a escala de Fazekas) detectadas na ressonância magnética (RMN) crânio-encefálica (CE) (9); e (iii) sem alteração da autonomia, determinada pela Escala de Actividades Instrumentais de Vida Diária (IADL) (10). Os doentes foram referenciados para o estudo por terem ASBC em tomografia axial computadorizada (TAC) ou RMN CE (8). Os participantes foram avaliados na inclusão e depois anualmente durante 3 anos, com um protocolo extenso que incluiu o registo das variáveis demográficas, dos factores de risco vasculares, da patologia concomitante, avaliação da depressão, da qualidade de vida, avaliação neurológica e médica e avaliação neuropsicológica. A avaliação clínica incluiu a classificação de defeito cognitivo de acordo com os critérios clínicos usuais (11). A RMN foi efectuada na inclusão e repetida após os 3 anos de seguimento. A inclusão dos participantes iniciou-se em Julho 2001, tendo sido incluídos 639 indivíduos (idade média 74.1 anos, SD 5.0, 55% género feminino, 9.6 anos de nível de escolaridade, SD 3.8). Da amostra inicial, 89% (568), 78.4% (501), e 75% (480) dos participantes foram seguidos nas visitas clínicas de mês 12, 24 e 36, respectivamente. Após um período de seguimento médio de 2.9 anos, obteve-se informação da transição de completa autonomia para incapacidade em 633 (99%) participantes. Quarenta e três participantes morreram (6.7% da amostra inicial) até ao 3º de seguimento. Cinquenta e um participantes faltaram a todas as visitas clínicas de seguimento. Para estes cinquenta e um participantes não foi possível atribuir um diagnóstico de estado cognitivo no seguimento, apesar de ser conhecido o estado vital e funcional. Considerando os diagnóstico cognitivos efectuados na última visita clínica, foi feito diagnóstico de demência em 90 participantes (Demência vascular, 54; doença de Alzheimer, 22; doença de Alzheimer com componente vascular, 12; Demência fronto-temporal, 2), e foi efectuado diagnóstico de defeito cognitivo não demência em 147 participantes (Defeito cognitivo vascular sem critérios de demência - CIND, 86; Defeito cognitivo ligeiro - MCI, 61). O nosso estudo mostrou que: 1. A gravidade das ASBC se relaciona com pior desempenho nas medidas globais de cognição, nas funções executivas, na velocidade e controlo motor e em testes de atenção, nomeação, e capacidades visuo-construtivas em indivíduos idosos que vivem de forma independente. O impacto das ASBC no desempenho neuropsicológico manteve-se mesmo quando se controlou a análise para variáveis demográficas (idade e educação), factores de risco vascular e atrofia do lobo temporal. 2. A gravidade das ASBC é preditora de defeito cognitivo (demência e não demência) em indivíduos idosos com ASBC, ao longo do tempo. As ASBC e ter tido acidente vascular cerebral são preditores de demência vascular mas não de doença de Alzheimer, enquanto que a atrofia do lobo temporal é preditor de doença de Alzheimer e de demência vascular. Os factores de risco vascular (diabetes, hipertensão e acidente vascular cerebral prévio) surgiram como factores relevantes com influência no desempenho neuropsicológico em indivíduos idosos que vivem autonomamente, independentemente da gravidade das ASBC. Após 3 anos, a diabetes na inclusão foi o único factor que foi preditor de defeito cognitivo de qualquer tipo (demência e não demência).3. As queixas de memória de indivíduos idosos com ASBC são preditoras de doença de Alzheimer com e sem componente vascular ao longo do tempo, independentemente da presença de sintomas depressivos e do estado global cognitivo na inclusão. A elevada frequência de participantes com queixas de memória que desenvolveram doença de Alzheimer ao longo do seguimento reforçou a importância das queixas de memória nos idosos, mesmo que tenham evidência de doença de pequenos vasos cerebral. 4. Os sintomas depressivos estão associados a pior desempenho cognitivo (em medidas de avaliação cognitivas globais, funções executivas e velocidade) na inclusão e são preditores de posterior declínio cognitivo ao longo do seguimento. Estes resultados estão de acordo com a hipótese da “depressão vascular” para os sintomas depressivos de início tardio. Os sintomas depressivos poderiam ser a expressão de lesão vascular e não o resultado de uma patologia do humor. É ainda possível que os sintomas depressivos e as ASBC tenham um efeito aditivo ou sinergístico para o desenvolvimento de demência ao longo do tempo. 5. A actividade física reduz o risco de progressão para defeito cognitivo, especialmente demência vascular, mas não para doença de Alzheimer, em indivíduos idosos com ASBC. Uma das explicações possíveis para esta redução de risco pode ser o controlo dos factores de risco vascular, uma vez que a actividade física se associa a um estilo de vida mais saudável. Os nossos resultados apoiam a perspectiva de que os sujeitos idosos com factores de risco vascular e evidência de ASBC beneficiam de actividade física regular. O estudo tem algumas limitações, nomeadamente relacionadas com a selecção da amostra, que não foi retirada da comunidade. Os participantes foram seleccionados de consultas externas por terem ASBC de qualquer gravidade. A outra limitação prende-se com a evolução tecnológica, pois o estudo foi desenhado há 10 anos. No entanto, este estudo foi realizado numa amostra heterogénea de dimensão considerável, com uma abordagem rigorosa, sistemática e muito completa. Acresce ainda que apesar de alguma perda de informação na avaliação cognitiva ao longo do tempo, 99% da amostra inicial teve informação quanto ao estado vital e funcional no fim dos três anos de seguimento. Adicionalmente o seguimento foi suficiente para permitir conversão para defeito cognitivo incluindo demência, e um número considerável de participantes fez RMN de seguimento. Após este trabalho pensamos existir evidência suficiente para afirmar que as ASBC não são um achado inócuo associado à idade. Os nossos resultados indicam que as ASBC severas estão implicadas na transição para defeito cognitivo. Identificámos ainda vários factores de risco implicados na progressão para defeito cognitivo, como a diabetes e o AVC, que surgem como factores de potencial intervenção para prevenir demência. Os nossos resultados salientam ainda o papel do controlo de factores de risco vasculares como da actividade física na redução do risco cognitivo associado à idade. Infelizmente ainda não há dados que sustentem recomendações específicas quanto ao tipo de controlo dos factores de risco vascular e tipo de actividade física como preventiva do desenvolvimento de demência. Esta é uma área de claro interesse da investigação futura. Tais recomendações têm que partir de estudos intervencionais que controlem os marcadores imagiológicos vasculares. Estes devem incluir técnicas que permitam não só avaliar áreas de ASBC nas sequências convencionais como sequências que permitam maior sensibilidade de detecção de ASBC, quando os exames convencionais são aparentemente normais. Devem ainda incluir técnicas destinadas a avaliar outras alterações de pequenos vasos cerebrais, como micro-hemorragias e ser controlados para os potenciais factores confundentes (como a atrofia cerebral). Para este objectivo os estudos têm que ter dimensão suficiente, o que só nos parece possível numa base multicêntrica. Por último, as ASBC surgem como um potencial objectivo primário para estudos de intervenção na área dos ensaios cognitivos.The LADIS Study was partially supported by the European Union within the Vth European Framework Program ‘Quality of life and management of living resources’, between 1998 and 2002, contract No. QLRT-2000-0044

Endothelial biomarkers in critically-ill COVID-19 patients: potential predictors of the need for dialysis

Introduction: To evaluate the function of vascular biomarkers to predict need for hemodialysis in critically-ill patients with COVID-19. Methods: This is a prospective study with 58 critically-ill patients due to COVID-19 infection. Laboratory tests in general and vascular biomarkers, such as VCAM-1, Syndecan-1, Angiopoietin-1 and Angiopoeitin-2 were quantified on intensive care unit (ICU) admission. Results: There was a 40% death rate. VCAM and Ang-2/Ang-1 ratio on ICU admission were associated with need for hemodialysis. Vascular biomarkers (VCAM-1, Syndecan-1, angiopoetin-2/ anogiopoetin-1 ratio) were predictors of death and their cut-off values were useful to stratify patients with a worse prognosis. In the multivariate cox regression analysis with adjusted models, VCAM-1 [O.R. 1.13 (C.I. 95%: 1.01 - 1.27); p= 0.034] and Ang-2/Ang-1 ratio [O.R. 4.87 (C.I.95%: 1.732 - 13.719); p= 0.003] were associated with need for dialysis. Conclusion: Vascular biomarkers, mostly VCAM-1 and Ang-2/Ang-1 ratio, showed better efficiency to predict need for hemodialysis in critically-ill COVID-19 patients

Neurohumoral and ambulatory haemodynamic adaptations following isometric exercise training in unmedicated hypertensive patients

Objective: Hypertension remains the leading modifiable risk factor for cardiovascular disease (CVD). Isometric exercise training (IET) has been shown to be a useful non-pharmacological intervention for reducing resting blood pressure (BP). This study aimed to measure alterations in office BP, ambulatory BP, cardiac autonomic modulation and inflammatory and vascular biomarkers following a programme of IET in unmedicated hypertensive patients. Methods: Twenty-four unmedicated stage 1 hypertensive patients (age 43.8±7.3 years; height, 178.1±7 cm; weight 89.7±12.8 kg) were randomly assigned in a cross-over study design, to 4-weeks of home based IET and control period, separated by a 3-week washout period. Office and Ambulatory BP, cardiac autonomic modulation, and inflammatory and vascular biomarkers were recorded pre and post IET and control periods. Results: Clinic and 24-hour ambulatory BP significantly reduced following IET by 12.4/6.2 mmHg and 11.8/5.6 mmHg in systolic/diastolic BP, respectively (p<0.001 for both), compared to the control. The BP adaptations were associated with a significant (p=0.018) reduction in the average real variability of 24-hour ambulatory BP following IET, compared to control. Cardiac autonomic modulation improved by 11% (p<0.001), baroreceptor reflex sensitivity improved by 47% (p<0.001), and interleukin-6 and asymmetric dimethylarginine reduced by 10% (p=0.022) and 19% (p=0.023), respectively, which differed significantly to the control period. Conclusion: This is the first evidence of durable BP reduction and wider CVD risk benefits of IET in a relevant patient population. Our findings support the role of IET as a safe and viable therapeutic and preventative intervention in the treatment of HTN

ST2 and Multimarker Testing in Acute Decompensated Heart Failure

Most data on heart failure biomarkers have been derived from patient cohorts with chronic disease. However, risk prediction in patients admitted with acute decompensated heart failure (ADHF) remains a challenge. ADHF is not a single disease: it presents in various manners, and different causes may underlie ADHF, which may be reflected by different biomarkers. Soluble suppression of tumorigenicity 2 (ST2) has been shown to be a strong independent predictor of short-, mid-, and long-term outcome in ADHF. Furthermore, combining biomarkers may help further improve the prognostic power of ST2. The ProBNP Investigation of Dyspnea in the Emergency Department study showed that elevated plasma levels of ST2 together with elevated levels of 4 other biomarkers have clear incremental values to predict outcome in ADHF. The Multinational Observational Cohort on Acute Heart Failure study is an international collaborative network that recruited 5,306 patients hospitalized for ADHF that demonstrated that ST2 and midregional pro-adrenomedulin had independently strong value to predict 30-day and 1-year outcome in patients with ADHF. The Multinational Observational Cohort on Acute Heart Failure study also showed that C-reactive protein plus ST2 better classified risk in patients with ADHFs than ST2 alone. Combining biomarkers for risk prediction or risk stratification might have clinical and more importantly pathophysiological meaning