Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
1.
Microcirculation ; 28(8): e12731, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34569675

RESUMO

AIMS: Epidemiological studies should substantiate the paradigm that endothelial dysfunction contributes to the development of heart failure with preserved ejection fraction (HFpEF). We investigated the association of cardiac remodeling and dysfunction with peripheral vasoreactivity in the general population. METHODS: In 424 individuals, we echocardiographically assessed cardiac structure and function and determined digital vasomotor function by photoplethysmography (PPG) during reactive hyperemia (RH). We regressed echocardiographic indexes and abnormalities on RH ratios averaged for 30 s time intervals. We derived sex-specific peripheral vasoreactivity profiles from PPG time-series and compared their echocardiographic phenotypes. RESULTS: Higher left ventricular (LV) mass index and lower E/A ratio and e' peak and left atrial reservoir strain were independently related to lower RH ratios. Participants with LV hypertrophy or diastolic dysfunction presented significantly lower RH ratios during the 30 to 240s intervals than normal counterparts. Low RH responders (n = 250) presented higher odds for LV hypertrophy (adjusted OR: 2.60; p = .0040) and LV diastolic dysfunction (adjusted OR: 2.66; p = .0037) than moderate-to-high responders (n = 174). CONCLUSION: The association between subclinical heart maladaptation and decreased microvascular reactivity supports the involvement of endothelial dysfunction in HFpEF pathogenesis. Time-integrated profiling of microvascular vasoreactivity may enable early detection of HFpEF in the community.

2.
J Hypertens ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34475344

RESUMO

OBJECTIVES: This study aimed to evaluate the risk of all-cause mortality and incident cardiovascular disease associated with peak systolic blood pressure (PeakSBP) at clinical exercise testing. METHODS: Data from 10 096 clinical exercise tests (54% men, age 18-85 years) was cross-linked with outcome data from national registries. PeakSBP was compared with recently published reference percentiles as well as expressed as percentage predicted PeakSBP using reference equations.Natural cubic spline modelling and Cox regression were used to analyse data stratified by sex and baseline cardiovascular risk profile. RESULTS: Median [IQR] follow-up times were 7.9 [5.7] years (all-cause mortality) and 5.6 [5.9] years (incident cardiovascular disease), respectively. The adjusted risk of all-cause mortality [hazard ratio, 95% confidence interval (95% CI)] for individuals with PeakSBP below the 10th percentile was 2.00 (1.59-2.52) in men and 2.60 (1.97-3.44) in women, compared with individuals within the 10th--90th percentile. The corresponding risk for incident cardiovascular disease was 1.55 (1.28-1.89, men) and 1.34 (1.05-1.71, women). For males in the upper 90th percentile, compared with individuals within the 10th--90th percentile, the adjusted risks of all-cause death and incident cardiovascular disease were 0.35 (0.22-0.54) and 0.72 (0.57-0.92), respectively, while not statistically significant in women. Spline modelling revealed a continuous increase in risk with PeakSBP values less than 100% of predicted in both sexes, with no increase in risk more than 100% of predicted. CONCLUSION: Low, but not high, PeakSBP was associated with an increased risk of mortality and future cardiovascular disease. Using reference standards for PeakSBP could facilitate clinical risk stratification across patients of varying sex, age and exercise capacity.

3.
Am J Clin Nutr ; 114(5): 1655-1665, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34375388

RESUMO

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) serves protective functions in metabolic, cardiovascular, renal, and pulmonary diseases and is linked to COVID-19 pathology. The correlates of temporal changes in soluble ACE2 (sACE2) remain understudied. OBJECTIVES: We explored the associations of sACE2 with metabolic health and proteome dynamics during a weight loss diet intervention. METHODS: We analyzed 457 healthy individuals (mean ± SD age: 39.8 ± 6.6 y) with BMI 28-40 kg/m2 in the DIETFITS (Diet Intervention Examining the Factors Interacting with Treatment Success) study. Biochemical markers of metabolic health and 236 proteins were measured by Olink CVDII, CVDIII, and Inflammation I arrays at baseline and at 6 mo during the dietary intervention. We determined clinical and routine biochemical correlates of the diet-induced change in sACE2 (ΔsACE2) using stepwise linear regression. We combined feature selection models and multivariable-adjusted linear regression to identify protein dynamics associated with ΔsACE2. RESULTS: sACE2 decreased on average at 6 mo during the diet intervention. Stronger decline in sACE2 during the diet intervention was independently associated with female sex, lower HOMA-IR and LDL cholesterol at baseline, and a stronger decline in HOMA-IR, triglycerides, HDL cholesterol, and fat mass. Participants with decreasing HOMA-IR (OR: 1.97; 95% CI: 1.28, 3.03) and triglycerides (OR: 2.71; 95% CI: 1.72, 4.26) had significantly higher odds for a decrease in sACE2 during the diet intervention than those without (P ≤ 0.0073). Feature selection models linked ΔsACE2 to changes in α-1-microglobulin/bikunin precursor, E-selectin, hydroxyacid oxidase 1, kidney injury molecule 1, tyrosine-protein kinase Mer, placental growth factor, thrombomodulin, and TNF receptor superfamily member 10B. ΔsACE2 remained associated with these protein changes in multivariable-adjusted linear regression. CONCLUSIONS: Decrease in sACE2 during a weight loss diet intervention was associated with improvements in metabolic health, fat mass, and markers of angiotensin peptide metabolism, hepatic and vascular injury, renal function, chronic inflammation, and oxidative stress. Our findings may improve the risk stratification, prevention, and management of cardiometabolic complications.This trial was registered at clinicaltrials.gov as NCT01826591.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Composição Corporal , COVID-19/metabolismo , Dieta Redutora , Obesidade/metabolismo , Proteoma/metabolismo , Perda de Peso/fisiologia , Tecido Adiposo/metabolismo , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Inflamação , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Estresse Oxidativo , Pandemias , SARS-CoV-2 , Triglicerídeos/sangue , Programas de Redução de Peso
4.
ESC Heart Fail ; 8(4): 2928-2939, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34050710

RESUMO

AIMS: Biomarkers may provide insights into molecular mechanisms underlying heart remodelling and dysfunction. Using a targeted proteomic approach, we aimed to identify circulating biomarkers associated with early stages of heart failure. METHODS AND RESULTS: A total of 575 community-based participants (mean age, 57 years; 51.7% women) underwent echocardiography and proteomic profiling (CVD II panel, Olink Proteomics). We applied partial least squares-discriminant analysis (PLS-DA) and a machine learning algorithm [eXtreme Gradient Boosting (XGBoost)] to identify key proteins associated with echocardiographic abnormalities. We used Gaussian mixture modelling for unbiased clustering to construct phenogroups based on influential proteins in PLS-DA and XGBoost. Of 87 proteins, 13 were important in PLS-DA and XGBoost modelling for detection of left ventricular remodelling, left ventricular diastolic dysfunction, and/or left atrial reservoir dysfunction: placental growth factor, kidney injury molecule-1, prostasin, angiotensin-converting enzyme-2, galectin-9, cathepsin L1, matrix metalloproteinase-7, tumour necrosis factor receptor superfamily members 10A, 10B, and 11A, interleukins 6 and 16, and α1-microglobulin/bikunin precursor. Based on these proteins, the clustering algorithm divided the cohort into two distinct phenogroups, with each cluster grouping individuals with a similar protein profile. Participants belonging to the second cluster (n = 118) were characterized by an unfavourable cardiovascular risk profile and adverse cardiac structure and function. The adjusted risk of presenting echocardiographic abnormalities was higher in this phenogroup than in the other (P < 0.0001). CONCLUSIONS: We identified proteins related to renal function, extracellular matrix remodelling, angiogenesis, and inflammation to be associated with echocardiographic signs of early-stage heart failure. Proteomic phenomapping discriminated individuals at high risk for cardiac remodelling and dysfunction.


Assuntos
Insuficiência Cardíaca , Proteômica , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Placentário , Remodelação Ventricular
5.
Am J Cardiol ; 149: 132-139, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33757787

RESUMO

Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59 ± 11 years and 56% male sex), and compared with 31 age, sex and body mass index-matched normoglycemic controls. Cardiopulmonary exercise testing with resting followed by stress echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO2) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO2). Peripheral extraction was calculated as the ratio of VO2 to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain, E/e', and relative wall thickness. Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO2(<80%) and 18 (18%) presented abnormal VE/VCO2slope (>34). There was no significant difference in peak cardiac output; however, peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e' (beta = -0.24, p = 0.004) was associated with lower peak VO2 along with age, sex and body mass index (R2 = 0.53). A cluster analysis found left ventricular longitudinal strain, E/e', relative wall thickness and peak VO2 in different clusters. In conclusion, impaired peripheral extraction may contribute to reduced peak VO2in asymptomatic patients with DM. Furthermore, a cluster analysis suggests that cardiopulmonary exercise testing and echocardiography may be complementary for defining subclinical heart failure in patients with DM.


Assuntos
Débito Cardíaco/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/fisiopatologia , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Idoso , Doenças Assintomáticas , Índice de Massa Corporal , Estudos de Casos e Controles , Análise por Conglomerados , Diabetes Mellitus Tipo 2/metabolismo , Ecocardiografia sob Estresse , Teste de Esforço , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Hypertens Res ; 44(4): 446-453, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542474

RESUMO

Fractal analysis provides a global assessment of vascular networks (e.g., geometric complexity). We examined the association of diastolic left ventricular (LV) function with the retinal microvascular fractal dimension. A lower fractal dimension signifies a sparser retinal microvascular network. In 628 randomly recruited Flemish individuals (51.3% women; mean age, 50.8 years), we measured diastolic LV function by echocardiography and the retinal microvascular fractal dimension by the box-counting method (Singapore I Vessel Assessment software, version 3.6). The left atrial volume index (LAVI), e', E/e' and retinal microvascular fractal dimension averaged (±SD) 24.3 ± 6.2 mL/m2, 10.9 ± 3.6 cm/s, 6.96 ± 2.2, and 1.39 ± 0.05, respectively. The LAVI, E, e' and E/e' were associated (P < 0.001) with the retinal microvascular fractal dimension with association sizes (per 1 SD), amounting to -1.49 mL/m2 (95% confidence interval, -1.98 to -1.01), 2.57 cm/s (1.31-3.84), 1.34 cm/s (1.07-1.60), and -0.74 (-0.91 to -0.57), respectively. With adjustments applied for potential covariables, the associations of E peak and E/e' with the retinal microvascular fractal dimension remained significant (P ≤ 0.020). Over a median follow-up of 5.3 years, 18 deaths occurred. The crude and adjusted hazard ratios expressing the risk of all-cause mortality associated with a 1-SD increment in the retinal microvascular fractal dimension were 0.36 (0.23-0.57; P < 0.001) and 0.57 (0.34-0.96; P = 0.035), respectively. In the general population, a lower retinal microvascular fractal dimension was associated with greater E/e', a measure of LV filling pressure. These observations can potentially be translated into new strategies for the prevention of diastolic LV dysfunction.

7.
Sci Rep ; 11(1): 4067, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603036

RESUMO

Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for clinical intervention prior to actual disease presentation. We therefore determined the associations between exposure to multiple air pollutants and both immunological outcomes (methylation and protein expression of immune cell types associated with immune regulation) and cardiovascular outcomes (blood pressure) in a cohort of school-aged children (6-8 years; n = 221) living in a city with known elevated pollution levels. Exposure to fine particular matter (PM2.5), carbon monoxide (CO), and ozone (O3) was linked to altered methylation of most CpG sites for genes Foxp3, IL-4, IL-10 and IFN-g, all involved in immune regulation (e.g. higher PM2.5 exposure 1 month prior to the study visit was independently associated with methylation of the IL-4 CpG24 site (est = 0.16; P = 0.0095). Also, immune T helper cell types (Th1, Th2 and Th17) were associated with short-term exposure to PM2.5, O3 and CO (e.g. Th1 cells associated with PM2.5 at 30 days: est = - 0.34, P < 0.0001). Both B cells (est = - 0.19) and CD4+ cells (est = 0.16) were associated with 1 day NO2 exposure (P ≤ 0.031), whereas CD4+ and CD8+ cells were associated with chronic exposure to PAH456, NOx and/or NO2 (P ≤ 0.038 for all). Finally, diastolic BP (DBP) was inversely associated with long-term exposures to both CO and PAH456, and both systolic and pulse pressure were associated with short-term NO2 and chronic NOx exposure. Our findings demonstrate links between air pollution exposure and methylation of immunoregulatory genes, immune cell profiles and blood pressure, suggesting that even at a young age, the immune and cardiovascular systems are negatively impacted by exposure to air pollution.

9.
Am J Hypertens ; 34(1): 46-55, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32918813

RESUMO

BACKGROUND: Population studies investigating the contribution of immunometabolic disturbances to heart dysfunction remain scarce. We combined high-throughput biomarker profiling, multidimensional network analyses, and regression statistics to identify immunometabolic markers associated with subclinical heart dysfunction in the community. METHODS: In 1,236 individuals (mean age, 51.0 years; 51.5% women), we measured 39 immunometabolic markers and assessed echocardiographic indexes of left ventricular diastolic dysfunction (LVDD) and left atrial (LA) reservoir dysfunction. We used partial least squares (PLS) to filter the most relevant biomarkers related to the echocardiographic characteristics. Subsequently, we assessed the associations between the echocardiographic features and biomarkers selected in PLS while accounting for clinical confounders. RESULTS: Influential biomarkers in PLS of echocardiographic characteristics included blood sugar, γ-glutamyl transferase, d-dimer, ferritin, hemoglobin, interleukin (IL)-4, IL-6, and serum insulin and uric acid. In stepwise regression incorporating clinical confounders, higher d-dimer was independently associated with higher E/e' ratio and LA volume index (P ≤ 0.05 for all). In multivariable-adjusted analyses, the risk for LVDD increased with higher blood sugar and d-dimer (P ≤ 0.048). After full adjustment, higher serum insulin and serum uric acid were independently related to worse LA reservoir strain and higher risk for LA reservoir dysfunction (P ≤ 0.039 for all). The biomarker panels detected LVDD and LA reservoir dysfunction with 87% and 79% accuracy, respectively (P < 0.0001). CONCLUSIONS: Biomarkers of insulin resistance, hyperuricemia, and chronic low-grade inflammation were associated with cardiac dysfunction. These biomarkers might help to unravel cardiac pathology and improve the detection and management of cardiac dysfunction in clinical practice.


Assuntos
Função do Átrio Esquerdo/fisiologia , Biomarcadores , Ecocardiografia Doppler , Hipertensão , Resistência à Insulina , Disfunção Ventricular Esquerda , Doenças Assintomáticas/epidemiologia , Bélgica/epidemiologia , Biomarcadores/análise , Biomarcadores/sangue , Glicemia/análise , Ecocardiografia Doppler/métodos , Ecocardiografia Doppler/estatística & dados numéricos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Insulina/sangue , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Ácido Úrico/sangue , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/imunologia , Disfunção Ventricular Esquerda/metabolismo
10.
JAMA Cardiol ; 6(2): 214-218, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33175083

RESUMO

Importance: The Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) estimate the 10-year risk for symptomatic heart failure (HF) from routine clinical data. The PCP-HF score should detect asymptomatic individuals with cardiac maladaptation preceding HF symptoms for it to be a useful HF prediction tool in primary prevention. Objective: To assess the concordance between PCP-HF risk scoring and the presence of subclinical cardiac maladaptation in the community. Design, Setting, and Participants: This cross-sectional analysis included participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes who underwent a clinical examination including echocardiography between May 2005 and January 2015. Participants younger than 30 years, older than 79 years, had prevalent cardiovascular disease, and/or had suboptimal echocardiographic imaging quality were excluded. Analysis began February 2020 and ended April 2020. Exposures: Ten-year HF risk as calculated from routine clinical data using the PCP-HF. Based on tertile limits, participants were categorized as having low (≤0.4%), intermediate (0.4%-2.4%), and high (≥2.4%) 10-year HF risk score. Main Outcomes and Measures: Echocardiographic profiles of subclinical heart remodeling and dysfunction. Results: A total of 1020 individuals were analyzed (mean [SD] age, 52.8 [11.4] years; 541 female [53.0%]). The prevalence of left ventricular (LV) remodeling and dysfunction was significantly higher from low to intermediate and high 10-year HF risk score. A doubling in 10-year HF risk score was associated with higher odds for LV concentric remodeling (odds ratio [OR], 1.48; 95% CI, 1.36-1.61; P < .001), LV hypertrophy (OR, 1.66; 95% CI, 1.51-1.83; P < .001), abnormal LV longitudinal strain (OR, 1.12; 95% CI, 1.05-1.19; P < .001), and LV diastolic dysfunction (OR, 2.28; 95% CI, 1.94-2.69; P < .001). Moreover, the PCP-HF score detected echocardiographic abnormalities with an accuracy of 74% (LV concentric remodeling), 78% (LV hypertrophy), 59% (abnormal LV longitudinal strain), and 87% (LV diastolic dysfunction). The likelihood of LV concentric remodeling, hypertrophy, and diastolic dysfunction were 3.1, 3.8, and 9.4 times higher in participants with high 10-year HF risk score than the average population risk, respectively (P < .001). Of all PCP-HF score components, age, body mass index, and systolic blood pressure were key correlates of echocardiographic abnormalities in multivariable-adjusted analysis. Conclusions and Relevance: PCP-HF risk scoring adequately detected individuals with subclinical heart maladaptation that precedes HF symptoms by years. Thus, it may be a valuable HF prediction tool in primary prevention.

11.
J Hum Hypertens ; 35(1): 55-64, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32042073

RESUMO

Isometric handgrip exercise (IHG) triggers acute increases in cardiac output to meet the metabolic demands of the active skeletal muscle. An abnormal cardiovascular response to IHG might reflect early stages of cardiovascular disease. In a large community-based cohort, we comprehensively assessed the clinical correlates of acute cardiovascular changes during IHG. In total, 333 randomly recruited subjects (mean age, 53 ± 13 years, 45% women) underwent simultaneous echocardiography and finger applanation tonometry at rest and during 3 min of IHG at 40% maximal handgrip force. We calculated time-domain measures of short-term heart rate variability (HRV) from finger pulse intervals. We assessed the adjusted associations of changes in blood pressure (BP) and echocardiographic indexes with clinical characteristics and HRV measures. During IHG, men presented a stronger absolute increase in heart rate, diastolic BP, left ventricular (LV) volumes and cardiac output than women, even after adjustment for covariables. In adjusted continuous and categorical analyses, age correlated positively with the increase in systolic BP and pulse pressure, but negatively with the increase in LV stroke volume and cardiac output during exercise. After full adjustment, a greater increase in systolic and diastolic BP during exercise was associated with lower absolute real variability (P ≤ 0.026) and root mean square of successive differences (P ≤ 0.032) in pulse intervals at rest. In a general population sample, women presented a weaker cardiovascular response to IHG than men. Older age was associated with greater rise in BP pulsatility and diminished cardiac reserve. Low HRV at rest predicted a higher BP increase during isometric exercise.


Assuntos
Força da Mão , Contração Isométrica , Idoso , Pressão Sanguínea , Exercício Físico , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade
12.
Eur Heart J Cardiovasc Imaging ; 22(10): 1208-1217, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-32588036

RESUMO

AIMS: Both left ventricular (LV) diastolic dysfunction (LVDD) and hypertrophy (LVH) as assessed by echocardiography are independent prognostic markers of future cardiovascular events in the community. However, selective screening strategies to identify individuals at risk who would benefit most from cardiac phenotyping are lacking. We, therefore, assessed the utility of several machine learning (ML) classifiers built on routinely measured clinical, biochemical, and electrocardiographic features for detecting subclinical LV abnormalities. METHODS AND RESULTS: We included 1407 participants (mean age, 51 years, 51% women) randomly recruited from the general population. We used echocardiographic parameters reflecting LV diastolic function and structure to define LV abnormalities (LVDD, n = 252; LVH, n = 272). Next, four supervised ML algorithms (XGBoost, AdaBoost, Random Forest (RF), Support Vector Machines, and Logistic regression) were used to build classifiers based on clinical data (67 features) to categorize LVDD and LVH. We applied a nested 10-fold cross-validation set-up. XGBoost and RF classifiers exhibited a high area under the receiver operating characteristic curve with values between 86.2% and 88.1% for predicting LVDD and between 77.7% and 78.5% for predicting LVH. Age, body mass index, different components of blood pressure, history of hypertension, antihypertensive treatment, and various electrocardiographic variables were the top selected features for predicting LVDD and LVH. CONCLUSION: XGBoost and RF classifiers combining routinely measured clinical, laboratory, and electrocardiographic data predicted LVDD and LVH with high accuracy. These ML classifiers might be useful to pre-select individuals in whom further echocardiographic examination, monitoring, and preventive measures are warranted.


Assuntos
Hipertensão , Disfunção Ventricular Esquerda , Feminino , Humanos , Hipertrofia Ventricular Esquerda , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Disfunção Ventricular Esquerda/diagnóstico por imagem , Remodelação Ventricular
13.
J Card Fail ; 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34979242

RESUMO

BACKGROUND: The insulin like growth factor (IGF) axis emerged as an important pathway in heart failure with preserved ejection (HFpEF). We aimed to identify IGF phenotypes associated with HFpEF in the context high-dimensional proteomic profiling. METHODS: From the Intermountain INSPIRE Registry, we identified 96 patients with HFpEF and matched controls. We performed targeted proteomics including IGF-1,2, IGF binding proteins (IGFBP) 1-7 and 111 other proteins (EMD Millipore and ELISA). We used partial least square discriminant analysis (PLS-DA) to identify a set of proteins associated with prevalent HFpEF, pulmonary hypertension (PH) and 5-year-all-cause mortality. K-mean clustering was used to identify IGF phenotypes. RESULTS: Patients with HFpEF had a high prevalence of systemic hypertension (95%) and coronary artery disease (74%). Using PLS-DA, we identified a set of biomarkers including IGF1,2 and IGFBP-1,2,7 that provided a strong discrimination of HFPEF, PH and mortality with an AUC of 0.91, 0.77 and 0.83, respectively. Using K mean clustering, we identified three IGF phenotypes that were independently associated with all-cause 5-year mortality after adjustment for age, NT-proBNP and kidney disease (p=0.004). Multivariable analysis validated the prognostic value of IGFBP-1 and 2 in the CATHGEN biorepository. CONCLUSION: IGF phenotypes were associated with PH and mortality in HFpEF.

14.
Environ Health ; 19(1): 108, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066786

RESUMO

BACKGROUND: Childhood exposure to air pollution contributes to cardiovascular disease in adulthood. Immune and oxidative stress disturbances might mediate the effects of air pollution on the cardiovascular system, but the underlying mechanisms are poorly understood in adolescents. Therefore, we aimed to identify immune biomarkers linking air pollution exposure and blood pressure levels in adolescents. METHODS: We randomly recruited 100 adolescents (mean age, 16 years) from Fresno, California. Using central-site data, spatial-temporal modeling, and distance weighting exposures to the participant's home, we estimated average pollutant levels [particulate matter (PM), polyaromatic hydrocarbons (PAH), ozone (O3), carbon monoxide (CO) and nitrogen oxides (NOx)]. We collected blood samples and vital signs on health visits. Using proteomic platforms, we quantitated markers of inflammation, oxidative stress, coagulation, and endothelial function. Immune cellular characterization was performed via mass cytometry (CyTOF). We investigated associations between pollutant levels, cytokines, immune cell types, and blood pressure (BP) using partial least squares (PLS) and linear regression, while adjusting for important confounders. RESULTS: Using PLS, biomarkers explaining most of the variance in air pollution exposure included markers of oxidative stress (GDF-15 and myeloperoxidase), acute inflammation (C-reactive protein), hemostasis (ADAMTS, D-dimer) and immune cell types such as monocytes. Most of these biomarkers were independently associated with the air pollution levels in fully adjusted regression models. In CyTOF analyses, monocytes were enriched in participants with the highest versus the lowest PM2.5 exposure. In both PLS and linear regression, diastolic BP was independently associated with PM2.5, NO, NO2, CO and PAH456 pollution levels (P ≤ 0.009). Moreover, monocyte levels were independently related to both air pollution and diastolic BP levels (P ≤ 0.010). In in vitro cell assays, plasma of participants with high PM2.5 exposure induced endothelial dysfunction as evaluated by eNOS and ICAM-1 expression and tube formation. CONCLUSIONS: For the first time in adolescents, we found that ambient air pollution levels were associated with oxidative stress, acute inflammation, altered hemostasis, endothelial dysfunction, monocyte enrichment and diastolic blood pressure. Our findings provide new insights on pollution-related immunological and cardiovascular disturbances and advocate preventative measures of air pollution exposure.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Adolescente , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Biomarcadores/análise , Proteína C-Reativa/análise , California , Monóxido de Carbono/efeitos adversos , Monóxido de Carbono/análise , Células Endoteliais/metabolismo , Exposição Ambiental/análise , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Óxidos de Nitrogênio/efeitos adversos , Óxidos de Nitrogênio/análise , Estresse Oxidativo/efeitos dos fármacos , Ozônio/efeitos adversos , Ozônio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/análise , Proteômica , Ubiquitina-Proteína Ligases/sangue
15.
J Am Heart Assoc ; 9(15): e014305, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32750311

RESUMO

Background Prematurity disrupts the perinatal maturation of the microvasculature and macrovasculature and confers high risk of vascular dysfunction later in life. No previous studies have investigated the crosstalk between the microvasculature and macrovasculature in childhood. Methods and Results In a case-control study, we enrolled 55 children aged 11 years weighing <1000 g at birth and 71 matched controls (October 2014-November 2015). We derived central blood pressure (BP) wave by applanation tonometry and calculated the forward/backward pulse waves by an automated pressure-based wave separation algorithm. We measured the renal resistive index by pulsed wave Doppler and the central retinal arteriolar equivalent by computer-assisted program software. Compared with controls, patients had higher central systolic BP (101.5 versus 95.2 mm Hg, P<0.001) and backward wave amplitude (15.5 versus 14.2 mm Hg, P=0.029), and smaller central retinal arteriolar equivalent (163.2 versus 175.4 µm, P<0.001). In multivariable analyses, central retinal arteriolar equivalent was smaller with higher values (+1 SD) of central systolic BP (-2.94 µm; 95% CI, -5.18 to -0.70 µm [P=0.011]) and forward (-2.57 µm; CI, -4.81 to -0.32 µm [P=0.026]) and backward (-3.20 µm; CI, -5.47 to -0.94 µm [P=0.006]) wave amplitudes. Greater renal resistive index was associated with higher backward wave amplitude (0.92 mm Hg, P=0.036). Conclusions In childhood, prematurity compared with term birth is associated with higher central systolic BP and forward/backward wave amplitudes. Higher renal resistive index likely moves reflection points closer to the heart, thereby explaining the inverse association of central retinal arteriolar equivalent with central systolic BP and backward wave amplitude. These observations highlight the crosstalk between the microcirculation and macrocirculation in children. Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02147457.


Assuntos
Hemodinâmica/fisiologia , Rim/irrigação sanguínea , Microvasos/patologia , Nascimento Prematuro/patologia , Vasos Retinianos/patologia , Pressão Sanguínea , Estudos de Casos e Controles , Criança , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Ultrassonografia
16.
J Hypertens ; 38(12): 2465-2474, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32649644

RESUMO

OBJECTIVE: Echocardiographic definitions of subclinical left atrial dysfunction based on epidemiological data remain scarce. In this population study, we derived outcome-driven thresholds for echocardiographic left atrial function parameters discriminating between normal and abnormal values. METHODS: In 1306 individuals (mean age, 50.7 years; 51.6% women), we echocardiographically assessed left atrial function and LV global longitudinal strain. We derived cut-off values for left atrial emptying fraction (LAEF), left atrial function index (LAFI) and left atrial reservoir strain (LARS) to define left atrial dysfunction using receiver-operating curve threshold analysis. Main outcome was the incidence of cardiac events and atrial fibrillation (AFib) on average 8.5 years later. RESULTS: For prediction of new-onset AFib, left atrial cut-offs yielding the best balance between sensitivity and specificity (highest Youden index) were: LAEF less than 55%, LAFI less than 40.5 and LARS less than 23%. Applying these cut-offs, abnormal LAEF, LAFI and LARS were, respectively, present in 27, 37.1 and 18.1% of the cohort. Abnormal LARS (<23%) was independently associated with higher risk for cardiac events and new-onset AFib (P ≤ 0.012). Participants with both abnormal LAEF and LARS presented a significantly higher risk to develop cardiac events (hazard ratio: 2.10; P = 0.014) and AFib (hazard ratio: 6.45; P = 0.0036) than normal counterparts. The concomitant presence of an impaired LARS and LV global longitudinal strain improved prognostic accuracy beyond a clinical risk model for cardiac events and the CHARGE-AF Risk Score for AFib. CONCLUSION: Left atrial dysfunction based on outcome-driven thresholds predicted cardiac events and AFib independent of conventional risk factors. Screening for subclinical left atrial and LV systolic dysfunction may enhance cardiac disease prediction in the community.


Assuntos
Função do Átrio Esquerdo/fisiologia , Ecocardiografia , Átrios do Coração , Cardiopatias , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Eur Heart J Cardiovasc Imaging ; 21(8): 876-884, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32386203

RESUMO

AIMS: Resting echocardiography is a valuable method for detecting subclinical heart failure (HF) in patients with diabetes mellitus (DM). However, few studies have assessed the incremental value of diastolic stress for detecting subclinical HF in this population. METHODS AND RESULTS: Asymptomatic patients with Type 2 DM were prospectively enrolled. Subclinical HF was assessed using systolic dysfunction (left ventricular longitudinal strain <16% at rest and <19% after exercise in absolute value), abnormal cardiac morphology, or diastolic dysfunction (E/e' > 10). Metabolic equivalents (METs) were calculated using treadmill speed and grade, and functional capacity was assessed by percent-predicted METs (ppMETs). Among 161 patients studied (mean age of 59 ± 11 years and 57% male sex), subclinical HF was observed in 68% at rest and in 79% with exercise. Among characteristics, diastolic stress had the highest yield in improving detection of HF with 57% of abnormal cases after exercise and 45% at rest. Patients with revealed diastolic dysfunction during stress had significantly lower exercise capacity than patients with normal diastolic stress (7.3 ± 2.1 vs. 8.8 ± 2.5, P < 0.001 for peak METs and 91 ± 30% vs. 105 ± 30%, P = 0.04 for ppMETs). On multivariable modelling found that age (beta = -0.33), male sex (beta = 0.21), body mass index (beta = -0.49), and exercise E/e' >10 (beta = -0.17) were independently associated with peak METs (combined R2 = 0.46). A network correlation map revealed the connectivity of peak METs and diastolic properties as central features in patients with DM. CONCLUSION: Diastolic stress test improves the detection of subclinical HF in patients with diabetes mellitus.


Assuntos
Cardiomiopatias , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Idoso , Diabetes Mellitus Tipo 2/complicações , Diástole , Teste de Esforço , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda
18.
Eur J Prev Cardiol ; 27(9): 978-987, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31564136

RESUMO

AIMS: The association between peak systolic blood pressure (SBP) during exercise testing and outcome remains controversial, possibly due to the confounding effect of external workload (metabolic equivalents of task (METs)) on peak SBP as well as on survival. Indexing the increase in SBP to the increase in workload (SBP/MET-slope) could provide a more clinically relevant measure of the SBP response to exercise. We aimed to characterize the SBP/MET-slope in a large cohort referred for clinical exercise testing and to determine its relation to all-cause mortality. METHODS AND RESULTS: Survival status for male Veterans who underwent a maximal treadmill exercise test between the years 1987 and 2007 were retrieved in 2018. We defined a subgroup of non-smoking 10-year survivors with fewer risk factors as a lower-risk reference group. Survival analyses for all-cause mortality were performed using Kaplan-Meier curves and Cox proportional hazard ratios (HRs (95% confidence interval)) adjusted for baseline age, test year, cardiovascular risk factors, medications and comorbidities. A total of 7542 subjects were followed over 18.4 (interquartile range 16.3) years. In lower-risk subjects (n = 709), the median (95th percentile) of the SBP/MET-slope was 4.9 (10.0) mmHg/MET. Lower peak SBP (<210 mmHg) and higher SBP/MET-slope (>10 mmHg/MET) were both associated with 20% higher mortality (adjusted HRs 1.20 (1.08-1.32) and 1.20 (1.10-1.31), respectively). In subjects with high fitness, a SBP/MET-slope > 6.2 mmHg/MET was associated with a 27% higher risk of mortality (adjusted HR 1.27 (1.12-1.45)). CONCLUSION: In contrast to peak SBP, having a higher SBP/MET-slope was associated with increased risk of mortality. This simple, novel metric can be considered in clinical exercise testing reports.


Assuntos
Determinação da Pressão Arterial , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Teste de Esforço , Adulto , Idoso , Doenças Cardiovasculares/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Saúde dos Veteranos
19.
Am J Cardiol ; 125(2): 229-235, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31753313

RESUMO

The neutrophil to lymphocyte ratio (NLR) has been proposed as a simple and routinely obtained marker of inflammation. This study sought to determine whether the NLR on admission as well as NLR trajectory would be complementary to the Get with the Guidelines Heart Failure (GWTG-HF) risk score in patients hospitalized with acute heart failure with preserved ejection fraction (HFpEF).Using the Stanford Translational Research Database, we identified 443 patients between January 2002 and December 2013 hospitalized with acute HFpEF and with complete data of NLR both on admission and at discharge. The primary endpoint was all-cause mortality. Mean age was 77 ±â€¯16 years, 58% were female, with a high prevalence of diabetes mellitus (35.4%), coronary artery disease (58.2%), systemic hypertension (96.6%) and history of atrial fibrillation (57.5%). Over a median follow-up of 2.2 years, 121 (27.3%) patients died. The median NLR on admission was 6.5 (IQR 3.6 - 11.1); a majority of patients decreased their NLR during the course of hospitalization. On multivariable Cox modeling, both NLR on admission (HR 1.18 95% CI (1.00 - .38), p = 0.04) and absolute NLR trajectory (HR 1.26 95% CI (1.10 - 1.45), p = 0.001) were shown to be incremental to GWTG-HF risk score (p < 0.05) for outcome prediction. Adding the NLR or absolute NLR trajectory to the GWTG-HF risk score significantly improved the area under the operator-receiver curve and the reclassification up to 3 years after admission.This simple, readily available marker of inflammation may be useful when stratifying the risk of patients hospitalized with HFpEF.


Assuntos
Insuficiência Cardíaca/sangue , Hospitalização/estatística & dados numéricos , Linfócitos/patologia , Neutrófilos/patologia , Volume Sistólico/fisiologia , Doença Aguda , Idoso , Causas de Morte/tendências , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Contagem de Leucócitos , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
20.
Int J Cardiol ; 297: 67-74, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31623873

RESUMO

BACKGROUND: Echocardiography might enhance cardiovascular (CV) risk stratification beyond tools grading the risk for atherosclerotic CV diseases (ASCVD). We therefore studied the complementarity between the ASCVD risk score recommended by American cardiology societies and echocardiographic profiling in predicting adverse CV outcome in the community. METHODS: 984 community-dwelling individuals between 40 and 79 years old (51.3% women) underwent CV risk profiling and echocardiography. We estimated their 10-year ASCVD risk from baseline risk factors using the Pooled Cohort Equations. Participants were categorized as at low (<2.5%), borderline (2.5-<7.5%) or intermediate-to-high (≥7.5%) ASCVD risk. Main outcome was the incidence of CV events collected on average 7.5 years later. RESULTS: The probability for cardiac remodeling and/or dysfunction as assessed by echocardiography rose progressively with increasing 10-year ASCVD risk. During follow-up, 116 participants experienced at least one CV endpoint (15.8 events per 1000 person-years). With increasing 10-year ASCVD risk, the CV event rate increased stronger in participants with ≥1 LV abnormality at baseline. Indeed, in individuals with an intermediate-to-high ASCVD risk and ≥1 LV abnormality at baseline, the risk was significantly higher than the average population risk for a first CV event (HR: 3.00, P < 0.001). Adding the presence of ≥1 LV abnormality to a ASCVD risk score-based model yielded significant improvement in C-statistics (P = 0.024), integrated discrimination (P = 0.0085) and net reclassification (P < 0.001) for adverse CV events. CONCLUSIONS: Echocardiographic profiling enhanced CV risk stratification in individuals at intermediate-to-high ASCVD risk. Echocardiographic screening might supplement traditional ASCVD risk grading for CV disease prediction.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Remodelação Ventricular , Adulto , Idoso , Estudos de Coortes , Ecocardiografia , Feminino , Humanos , Incidência , Vida Independente , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...