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1.
Am J Cardiol ; 136: 156-163, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32946864

RESUMO

High sensitivity cardiac troponin T (hscTnT), soluble ST2 (sST2), N-terminal B-type natriuretic peptide (NT-proBNP), and galectin-3 are biomarkers of cardiac injury, stress, myocardial stretch, and fibrosis. Elevated levels are associated with poor outcomes. However, their association with cardiac mechanics in older persons is unknown. Associations between these biomarkers and cardiac mechanics derived from speckle tracking echocardiography, including left ventricular longitudinal strain (LVLS), early diastolic strain, and left atrial reservoir strain (LARS) were evaluated using standardized beta coefficients () in a cross sectional analysis with cardiac biomarkers in older patients without cardiovascular disease, low ejection fraction, or wall motion abnormalities. Biomarker associations with strain were attenuated by demographics and risk factors. In adjusted models, LVLS was associated with continuous measures of hscTnT (ß∧-0.06, p = 0.020), sST2 (ß∧ -0.05, p = 0.024) and NT-proBNP (ß∧ -0.06, p = 0.007). "High" levels (i.e., greater than prognostic cutpoint) of hscTnT (>13 ng/ml), sST2 (>35 ng/ml), and NT-proBNP (>190 pg/ml) were also associated with worse LVLS. In risk factor adjusted models, LARS was associated with hscTnT (ß∧ -0.08, p = 0.003) and NT-proBNP (ß∧-0.18, p <0.0001). High hscTnT (>13 ng/ml) and high NT-proBNP (>190 pg/ml) were also both associated with worse LARS. Gal-3 was not associated with any strain measure. In conclusion, in persons ≥ 65 years of age, without cardiovascular disease, low ejection fraction, or wall motion abnormalities, hscTnT, sST2, and NT-proBNP are associated with worse LVLS. HscTnT and NT-proBNP are associated with worse LARS. In conclusion, these subclinical increases in blood biomarkers, and their associations with subtle diastolic and systolic dysfunction, may represent pre-clinical heart failure.

2.
J Am Coll Cardiol ; 76(12): 1455-1465, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32943164

RESUMO

BACKGROUND: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear. OBJECTIVES: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF. METHODS: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio. RESULTS: Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001). CONCLUSIONS: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.

3.
J Card Fail ; 26(11): 1006-1010, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32750485

RESUMO

BACKGROUND: Under controlled conditions, mental stress can provoke decrements in ventricular function, yet little is known about the effect of mental stress on diastolic function in patients with heart failure (HF). METHODS AND RESULTS: Twenty-four patients with HF with ischemic cardiomyopathy and reduced ejection fraction (n = 23 men; mean left ventricular [LV] ejection fraction 27 ± 9%; n = 13 with baseline elevated E/e') completed daily assessment of perceived stress, anger, and negative emotion for 7 days, followed by a laboratory mental stress protocol. Two-dimensional Doppler echocardiography was performed at rest and during sequential anger recall and mental arithmetic tasks to assess indices of diastolic function (E, e', and E/e'). Fourteen patients (63.6%) experienced stress-induced increases in E/e', with an average baseline to stress change of 6.5 ± 9.3, driven primarily by decreases in early LV relaxation (e'). Age-adjusted linear regression revealed an association between 7-day anger and baseline E/e'; patients reporting greater anger in the week before mental stress exhibited higher resting LV diastolic pressure. CONCLUSIONS: In patients with HF with reduced ejection fraction, mental stress can provoke acute worsening of LV diastolic pressure, and recent anger is associated with worse resting LV diastolic pressure. In patients vulnerable to these effects, repeated stress exposures or experiences of anger may have implications for long-term outcomes.

4.
Neurology ; 95(14): e1941-e1950, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32732296

RESUMO

OBJECTIVE: To test the hypothesis that orthostatic hypotension (OH) might cause cerebral hypoperfusion and injury, we examined the longitudinal relationship between OH or orthostatic symptoms and incident neurologic outcomes in a community population of older adults. METHODS: Cardiovascular Health Study participants (≥65 years) without dementia or stroke had blood pressure (BP) measured after lying down for 20 minutes and after standing 3 for minutes. Participants reported dizziness immediately upon standing and any dizziness in the past 2 weeks. OH was defined as a drop in standing systolic/diastolic BP ≥20/≥10 mm Hg. We determined the association between OH or dizziness with (1) MRI brain findings (ventricular size, white matter hyperintensities, brain infarcts) using linear or logistic regression, (2) cognitive function (baseline and over time) using generalized estimating equations, and (3) prospective adjudicated events (dementia, stroke, death) using Cox models. Models were adjusted for demographic characteristics and OH risk factors. We used multiple imputation to account for missing OH or dizziness (n = 534). RESULTS: Prior to imputation, there were 5,007 participants (mean age 72.7 ± 5.5 years, 57.6% women, 10.9% Black, 16% with OH). OH was modestly associated with death (hazard ratio [HR] 1.11; 95% confidence interval 1.02-1.20), but not MRI findings, cognition, dementia, or stroke. In contrast, dizziness upon standing was associated with lower baseline cognition (ß = -1.20; -1.94 to -0.47), incident dementia (HR 1.32; 1.04-1.62), incident stroke (HR 1.22; 1.06-1.41), and death (HR 1.13; 1.06-1.21). Similarly, dizziness over the past 2 weeks was associated with higher white matter grade (ß = 0.16; 0.03-0.30), brain infarcts (OR 1.31; 1.06-1.63), lower baseline cognition (ß = -1.18; -2.01 to -0.34), and death (HR 1.13; 1.04-1.22). CONCLUSIONS: Dizziness was more consistently associated with neurologic outcomes than OH 3 minutes after standing. Delayed OH assessments may miss pathologic information related to cerebral injury.


Assuntos
Encéfalo/patologia , Cognição/fisiologia , Tontura , Hipotensão Ortostática , Idoso , Demência/epidemiologia , Tontura/fisiopatologia , Feminino , Humanos , Hipotensão Ortostática/fisiopatologia , Masculino , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
5.
J Card Fail ; 26(5): 410-419, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32165348

RESUMO

BACKGROUND: CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults. METHODS AND RESULTS: We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as HF with preserved ejection fraction [HFpEF] and 419 as HF with reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (hazard ratio [HR]: 1.56 per doubling, 95% confidence interval [CI]: 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling: 1.10, 95% CI: 1.06-1.15), IL-6 (HR: 1.18, 95% CI: 1.10-1.25), and WBC (HR: 1.24, 95% CI: 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR: 1.50, 95% CI: 1.07-2.10) but not HFrEF (HR: 0.99, 95% CI: 0.67-1.49). CONCLUSIONS: Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications.

6.
Nat Commun ; 11(1): 163, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919418

RESUMO

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.


Assuntos
Fibrilação Atrial/genética , Cardiomiopatias/genética , Doença da Artéria Coronariana/genética , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Função Ventricular Esquerda/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Cardiomiopatias/patologia , Proteínas de Transporte/genética , Estudos de Casos e Controles , Inibidor de Quinase Dependente de Ciclina p21/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Proteínas dos Microfilamentos/genética , Proteínas Musculares/genética , Fatores de Risco
8.
J Am Heart Assoc ; 8(7): e010868, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30912456

RESUMO

Background Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation ( AF ). Conversely, whites may have a lower risk of heart failure ( CHF ). N-terminal pro-B-type natriuretic peptide ( NT -pro BNP) levels are higher in whites, predict incident AF , and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NT -pro BNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT -pro BNP . The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT -pro BNP ( CHS : 40% higher than blacks; 95% CI , 29-53; ARIC : 39% higher; 95% CI , 33-46) and had a greater risk of incident AF compared with blacks ( CHS : adjusted hazard ratio, 1.60; 95% CI , 1.31-1.93; ARIC : hazard ratio, 1.93; 95% CI , 1.57-2.27). NT -pro BNP levels explained a significant proportion of the racial difference in AF risk ( CHS : 36.2%; 95% CI , 23.2-69.2%; ARIC : 24.6%; 95% CI , 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI , 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI , 0.94-1.23), CHF -related mediation analyses were not performed. Conclusions A substantial portion of the relationship between race and AF was statistically explained by baseline NT -pro BNP levels. No consistent relationship between race and CHF was observed.


Assuntos
Afro-Americanos , Fibrilação Atrial/etnologia , Grupo com Ancestrais do Continente Europeu , Insuficiência Cardíaca/etnologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/epidemiologia , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia
9.
JACC Heart Fail ; 6(8): 701-709, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30007554

RESUMO

OBJECTIVES: This study evaluated the associations of obesity and cardiometabolic traits with incident heart failure with preserved versus reduced ejection fraction (HFpEF vs. HFrEF). Given known sex differences in HF subtype, we examined men and women separately. BACKGROUND: Recent studies suggest that obesity confers greater risk of HFpEF versus HFrEF. Contributions of associated metabolic traits to HFpEF are less clear. METHODS: We studied 22,681 participants from 4 community-based cohorts followed for incident HFpEF versus HFrEF (ejection fraction ≥50% vs. <50%). We evaluated the association of body mass index (BMI) and cardiometabolic traits with incident HF subtype using Cox models. RESULTS: The mean age was 60 ± 13 years, and 53% were women. Over a median follow-up of 12 years, 628 developed incident HFpEF and 835 HFrEF. Greater BMI portended higher risk of HFpEF compared with HFrEF (hazard ratio [HR]: 1.34 per 1-SD increase in BMI; 95% confidence interval [CI]: 1.24 to 1.45 vs. HR: 1.18; 95% CI: 1.10 to 1.27). Similarly, insulin resistance (homeostatic model assessment of insulin resistance) was associated with HFpEF (HR: 1.20 per 1-SD; 95% CI: 1.05 to 1.37), but not HFrEF (HR: 0.99; 95% CI: 0.88 to 1.11; p < 0.05 for difference HFpEF vs. HFrEF). We found that the differential association of BMI with HFpEF versus HFrEF was more pronounced among women (p for difference HFpEF vs. HFrEF = 0.01) when compared with men (p = 0.34). CONCLUSIONS: Obesity and related cardiometabolic traits including insulin resistance are more strongly associated with risk of future HFpEF versus HFrEF. The differential risk of HFpEF with obesity seems particularly pronounced among women and may underlie sex differences in HF subtypes.


Assuntos
Insuficiência Cardíaca/epidemiologia , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Volume Sistólico , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Colesterol/sangue , HDL-Colesterol/sangue , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores Sexuais , Triglicerídeos/sangue
10.
JACC Heart Fail ; 6(8): 678-685, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30007560

RESUMO

OBJECTIVES: This study aimed to determine temporal trends in the incidence of and mortality associated with heart failure (HF) and its subtypes (heart failure with reduced ejection fraction [HFrEF] and heart rate with preserved ejection fraction [HFpEF]) in the community. BACKGROUND: Major shifts in cardiovascular disease risk factor prevalence and advances in therapies may have influenced HF incidence and mortality. METHODS: In the FHS (Framingham Heart Study) and CHS (Cardiovascular Health Study), for participants who were ≥60 years of age and free of HF (n = 15,217; 60% women; 2,524 incident HF cases; 115,703 person-years of follow-up), we estimated adjusted incidence rate ratios of HF, HFrEF, and HFpEF from 1990 to 1999 and 2000 to 2009. We compared the cumulative incidence of and mortality associated with HFrEF versus HFpEF within and between decades. RESULTS: Across the 2 decades, HF incidence rate ratio was similar (p = 0.13). The incidence rate ratio of HFrEF declined (p = 0.0029), whereas HFpEF increased (p < 0.001). Although HFrEF incidence declined more in men than in women, men had a higher incidence of HFrEF than women in each decade (p < 0.001). The incidence of HFpEF significantly increased over time in both men and women (p < 0.001 and p = 0.02, respectively). During follow-up after HF, 1,701 individuals died (67.4%; HFrEF, n = 557 [33%]; HFpEF, n = 474 [29%]). There were no significant differences in mortality rates (overall, cardiovascular disease, and noncardiovascular disease) across decades within HF subtypes or between HFrEF and HFpEF within decade. CONCLUSIONS: In several U.S. community-based samples from 1990 to 2009, we observed divergent trends of decreasing HFrEF and increasing HFpEF incidence, with stable overall HF incidence and high risk for mortality. Our findings highlight the need to elucidate factors contributing to these observations.


Assuntos
Insuficiência Cardíaca/epidemiologia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Crescimento Demográfico , Estados Unidos/epidemiologia
11.
Am Heart J ; 197: 62-69, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29447785

RESUMO

BACKGROUND: Multiple prospective studies have established an association between inflammation and higher risk of atrial fibrillation (AF), but the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity and incident AF has not been extensively evaluated. METHODS: Using data from 10,794 Atherosclerosis Risk In Communities (ARIC) study participants aged 53-75 years, 5,181 Cardiovascular Health Study (CHS) participants aged 65 to 100 years, and 5,425 Multi-Ethnic Study of Atherosclerosis (MESA) participants aged 45-84 years, we investigated the association between baseline Lp-PLA2 levels and the risk of developing AF. Incident AF was identified in each cohort by follow-up visit electrocardiograms, hospital discharge coding of AF, or Medicare claims data. RESULTS: Over a mean of 13.1, 11.5, and 10.0 years of follow-up, 1,439 (13%), 2,084 (40%), and 615 (11%) incident AF events occurred in ARIC, CHS, and MESA, respectively. In adjusted analyses, each SD increment in Lp-PLA2 activity was associated with incident AF in both ARIC (hazard ratio [HR] 1.13, 95% CI 1.06-1.20) and MESA (HR 1.24, 95% CI 1.05-1.46). Each SD increment in Lp-PLA2 mass was also associated with incident AF in MESA (HR 1.25, 95% CI 1.11-1.41). No significant associations were observed among CHS participants. CONCLUSIONS: Although higher Lp-PLA2 mass and activity were associated with development of AF in ARIC and MESA, this relationship was not observed in CHS, a cohort of older individuals.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Fibrilação Atrial , Ativação Plaquetária/fisiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Correlação de Dados , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Incidência , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco , Estados Unidos
12.
Circulation ; 137(17): 1814-1823, 2018 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-29352072

RESUMO

BACKGROUND: Lifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known. METHODS: Participant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks. RESULTS: We included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction. CONCLUSIONS: Lifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to improve population-level HF prevention and control.


Assuntos
Grupos de Populações Continentais , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico , Função Ventricular Esquerda , Afro-Americanos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Europeu , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Hispano-Americanos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Infarto do Miocárdio/fisiopatologia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Estados Unidos/epidemiologia
13.
JAMA Cardiol ; 3(3): 215-224, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29322198

RESUMO

Importance: Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood. Objective: To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population. Design, Setting, and Participants: This study included 4 longitudinal community-based cohorts: the Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017. Exposures: The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6. Main Outcomes and Measures: Development of incident HFpEF and incident HFrEF. Results: Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95% CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95% CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95% CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95% CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95% CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95% CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95% CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95% CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95% CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95% CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95% CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF. Conclusions and Relevance: Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.


Assuntos
Biomarcadores/metabolismo , Insuficiência Cardíaca/diagnóstico , Adulto , Idoso , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Volume Sistólico/fisiologia
14.
Eur J Heart Fail ; 20(4): 651-659, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29226491

RESUMO

AIMS: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community. METHODS AND RESULTS: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78). CONCLUSIONS: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Medição de Risco , Volume Sistólico/fisiologia , Idoso , Causas de Morte/tendências , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
15.
J Am Heart Assoc ; 6(8)2017 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28775064

RESUMO

BACKGROUND: Atrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12-lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12-lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality. METHODS AND RESULTS: We utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12 years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15 792 participants over a median of 22 years. In the CHS, multivariable analyses revealed that a baseline 12-lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3-2.0; P<0.001) and a premature ventricular contraction predicted a 30% increased risk of heart failure (hazard ratio, 1.3; 95% CI, 1.0-1.6; P=0.021). In the negative control analyses, neither predicted incident myocardial infarction. A premature atrial contraction was associated with a 30% increased risk of death (hazard ratio, 1.3; 95% CI, 1.1-1.5; P=0.008) and a premature ventricular contraction was associated with a 20% increased risk of death (hazard ratio, 1.2; 95% CI, 1.0-1.3; P=0.044). Similarly statistically significant results for each analysis were also observed in ARIC. CONCLUSIONS: Based on a single standard ECG, a premature atrial contraction predicted incident atrial fibrillation and death and a premature ventricular contraction predicted incident heart failure and death, suggesting that this commonly used test may predict future disease.


Assuntos
Complexos Atriais Prematuros/mortalidade , Cardiomiopatias/mortalidade , Complexos Ventriculares Prematuros/mortalidade , Idoso , Fibrilação Atrial/mortalidade , Eletrocardiografia , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
16.
J Am Heart Assoc ; 6(7)2017 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-28735291

RESUMO

BACKGROUND: Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury). METHODS AND RESULTS: The Cardiovascular Health Study Cognition Study was a continuation of the Cardiovascular Health Study limited to the Pittsburgh, PA, center from 1998-1999 to 2014. In 1992-1994, 924 participants underwent magnetic resonance imaging of the brain. There were 199 deaths and 116 developed dementia before 1998-1999. Of the 609 participants eligible for the Pittsburgh Cardiovascular Health Study Cognition Study, 87.5% (n=532) were included in the study. There were 120 incident HF cases and 72% had dementia. In 80 of 87, dementia preceded HF. A combination of low coronary artery calcium score and low high-sensitivity cardiac troponin T was significantly associated with reduced risk of dementia and HF. CONCLUSIONS: Most participants with HF had dementia but with onset before HF. Lower high-sensitivity cardiac troponin T and coronary artery calcium was associated with low risk of dementia based on a small number of events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.


Assuntos
Envelhecimento , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Demência/epidemiologia , Insuficiência Cardíaca/epidemiologia , Coração/fisiopatologia , Nefropatias/epidemiologia , Rim/fisiopatologia , Calcificação Vascular/epidemiologia , Fatores Etários , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Aterosclerose/diagnóstico , Aterosclerose/mortalidade , Aterosclerose/fisiopatologia , Biomarcadores/sangue , Causas de Morte , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Cistatina C/sangue , Demência/diagnóstico , Demência/mortalidade , Demência/fisiopatologia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Nefropatias/diagnóstico , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Peptídeo Natriurético Encefálico/sangue , Testes Neuropsicológicos , Pennsylvania/epidemiologia , Fragmentos de Peptídeos/sangue , Prevalência , Fatores de Risco , Fatores de Tempo , Troponina T/sangue , Calcificação Vascular/diagnóstico , Calcificação Vascular/mortalidade , Calcificação Vascular/fisiopatologia
18.
Arch Osteoporos ; 12(1): 52, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28560501

RESUMO

Associations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found. INTRODUCTION: The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse. METHODS: We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression. RESULTS: Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01-1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant. CONCLUSION: These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends.


Assuntos
Densidade Óssea/fisiologia , Calcinose/fisiopatologia , Doenças das Valvas Cardíacas/fisiopatologia , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/fisiopatologia , Calcinose/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Colo do Fêmur/fisiopatologia , Doenças das Valvas Cardíacas/epidemiologia , Articulação do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estenose da Valva Mitral/epidemiologia , Estenose da Valva Mitral/fisiopatologia , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Prevalência , Fatores Sexuais , Estados Unidos/epidemiologia
20.
Am J Cardiol ; 119(6): 923-928, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28073429

RESUMO

We evaluated the association between 2-dimensional (2D) echocardiography (echo)-determined myocardial contraction fraction (MCF) and adverse cardiovascular outcomes including incident heart failure (HF), atherosclerotic cardiovascular disease (ASCVD), and mortality. The MCF, the ratio of left ventricular (LV) stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that can distinguish pathologic from physiological hypertrophy. Using 2D echo-guided M-mode data from the Cardiovascular Health Study, we calculated MCF in subjects with LV ejection fraction (EF) ≥55% and used Cox models to evaluate its association with incident HF, ASCVD, and all-cause mortality after adjusting for clinical and echo parameters. We assessed whether log2(SV) and log2(MV) were consistent with the expected 1:-1 ratio used in the definition of MCF. Among 2,147 participants (age 72 ± 5 years), average MCF was 59 ± 13%. After controlling for clinical and echo variables, each 10% absolute increment in MCF was associated with lower risk of HF (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82, 0.94), ASCVD (HR 0.90; 95% CI 0.85, 0.95), and death (HR 0.93; 95% CI 0.89, 0.97). Moreover, the MCF was still significantly associated with ASCVD and mortality, but not HF, after adjustment for percent-predicted LV mass. Significant departure from the 1:-1 ratio was not observed for ASCVD or death, but did occur for HF, driven by a stronger association for MV than SV. In conclusion, among older adults without CVD or low LV ejection fraction, 2D echo-guided M-mode-derived MCF was independently associated with lower risk of adverse cardiovascular outcomes, but this ratiometric index may not capture the full relation that is apparent when its components are modeled separately in the case of HF.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Idoso , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Estados Unidos/epidemiologia
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