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1.
JACC Clin Electrophysiol ; 6(1): 70-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31971908

RESUMO

OBJECTIVES: This study evaluated whether plasma miRNAs were specifically associated with sudden cardiac and/or arrhythmic death (SCD) in a cohort of patients with coronary heart disease (CHD), most of whom were without primary prevention implantable cardioverter-defibrillators. BACKGROUND: Novel biomarkers for sudden death risk stratification are needed in patients with CHD to more precisely target preventive therapies, such as implantable cardioverter-defibrillators. miRNAs have been implicated in regulating inflammation and cardiac fibrosis in cells, and plasma miRNAs have been shown to predict cardiovascular death in patients with CHD. METHODS: We performed a nested case control study within a multicenter cohort of 5,956 patients with CHD followed prospectively for SCD. Plasma levels of 18 candidate miRNAs previously associated with cardiac remodeling were measured in 129 SCD cases and 258 control subjects matched on age, sex, race, and left ventricular ejection fraction. RESULTS: miR-150-5p, miR-29a-3p, and miR-30a-5p were associated with increased SCD risk (odds ratios and 95% confidence intervals: 2.03 [1.12 to 3.67]; p = 0.02; 1.93 [1.07 to 3.50]; p = 0.02; 0.55 [0.31 to 0.97]; p = 0.04, respectively, for third vs. first tertile miRNA level). Unfavorable levels of all 3 miRNAs was associated with a 4.8-fold increased SCD risk (1.59 to 14.51; p = 0.006). A bioinformatics-based approach predicted miR-150-5p, miR-29a-3p, and miR-30a-5p to be involved in apoptosis, fibrosis, and inflammation. CONCLUSIONS: These findings suggest that plasma miRNAs may regulate pathways important for remodeling and may be useful in identifying patients with CHD at increased risk of SCD.

2.
Angiology ; 71(1): 17-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31129986

RESUMO

The Middle East and North Africa (MENA) region has a high burden of morbidity and mortality due to premature (≤55 years in men; ≤65 years in women) myocardial infarction (MI) and acute coronary syndrome (ACS). Despite this, the prevalence of risk factors in patients presenting with premature MI or ACS is incompletely described. We compared lifestyle, clinical risk factors, and biomarkers associated with premature MI/ACS in the MENA region with selected non-MENA high-income countries. We identified English-language, peer-reviewed publications through PubMed (up to March 2018). We used the World Bank classification system to categorize countries. Patients with premature MI/ACS in the MENA region had a higher prevalence of smoking than older patients with MI/ACS but a lower prevalence of diabetes, hypertension, and dyslipidemia. Men with premature MI/ACS had a higher prevalence of smoking than women but a lower prevalence of diabetes and hypertension. The MENA region had sparse data on lifestyle, diet, psychological stress, and physical activity. To address these knowledge gaps, we initiated the ongoing Gulf Population Risks and Epidemiology of Vascular Events and Treatment (Gulf PREVENT) case-control study to improve primary and secondary prevention of premature MI in the United Arab Emirates, a high-income country in the MENA region.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Infarto do Miocárdio/epidemiologia , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/prevenção & controle , África do Norte/epidemiologia , Idade de Início , Idoso , Estudos de Casos e Controles , Comorbidade , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Mortalidade Prematura , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Prevalência , Prevenção Primária , Prognóstico , Projetos de Pesquisa , Fatores de Risco , Prevenção Secundária , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia
3.
JAMA Intern Med ; 179(7): 898-905, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31135812

RESUMO

Importance: Recent guidelines have recommended nonfasting for routine testing of lipid levels based on comparisons of nonfasting and fasting populations. However, no previous study has examined the association of cardiovascular outcomes with fasting vs nonfasting lipid levels measured in the same individuals. Objective: To compare the association of nonfasting and fasting lipid levels with prospectively ascertained coronary and vascular outcomes and to evaluate whether a strategy of using nonfasting instead of fasting lipid level measurement would result in misclassification of risk for individuals undergoing evaluation for initiation of statin therapy. Design, Setting, and Participants: This post hoc prospective follow-up of a randomized clinical trial included 8270 of 10 305 participants from the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) with nonfasting and fasting lipid levels measured 4 weeks apart (including 6855 participants with no prior vascular disease) (median follow-up, 3.3 years; interquartile range, 2.8-3.6 years). Data were collected from February 1, 1998, to December 31, 2002, and analyzed from February 1, 2016, to November 30, 2018. Multivariable Cox models, adjusted for cardiovascular risk factors, were calculated for 40-mg/dL (1-mmol/L) higher values of nonfasting and fasting lipids. Main Outcomes and Measures: The trial's primary end point consisted of major coronary events (nonfatal myocardial infarction [MI] and fatal coronary heart disease [212 events]). Secondary analyses examined atherosclerotic cardiovascular disease (ASCVD) events (including MI, stroke, and ASCVD death [351 events]). Results: Among the 8270 participants (82.1% male; mean [SD] age, 63.4 [8.5] years), nonfasting samples had modestly higher triglyceride levels and similar cholesterol levels compared to fasting samples. Associations of nonfasting lipid levels with coronary events were similar to those for fasting lipid levels. For example, adjusted hazard ratios (HRs) per 40-mg/dL of low-density lipoprotein cholesterol were 1.32 (95% CI, 1.08-1.61; P = .007) for nonfasting levels and 1.28 (95% CI, 1.07-1.55; P = .008) for fasting levels. For the primary prevention group, adjusted HRs were 1.42 (95% CI, 1.13-1.78; P = .003) for nonfasting levels and 1.37 (95% CI, 1.11-1.69; P = .003) for fasting levels. Results were consistent by randomized treatment arm (atorvastatin calcium, 10 mg/d, or placebo) and similar for ASCVD events. Concordance of fasting and nonfasting lipid levels for classifying participants into appropriate ASCVD risk categories was high (94.8%). Conclusions and Relevance: Measurement of nonfasting and fasting lipid levels yields similar results in the same individuals for association with incident coronary and ASCVD events. These results suggest that routine measurement of nonfasting lipid levels may help facilitate ASCVD risk screening and treatment, including consideration of when to initiate statin therapy.

4.
JAMA Cardiol ; 3(7): 591-600, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29801082

RESUMO

Importance: The majority of sudden and/or arrhythmic deaths (SAD) in patients with coronary heart disease occur in those without severe systolic dysfunction, for whom strategies for sudden death prevention are lacking. Objective: To provide contemporary estimates of SAD vs other competing causes of death in patients with coronary heart disease without severe systolic dysfunction to search for high-risk subgroups that might be targeted in future trials of SAD prevention. Design, Setting, and Participants: This prospective observational cohort study included 135 clinical sites in the United States and Canada. A total of 5761 participants with coronary heart disease who did not qualify for primary prevention implantable cardioverter defibrillator therapy based on left ventricular ejection fraction (LVEF) of more than 35% or New York Heart Association (NYHA) heart failure class (LVEF >30%, NYHA I). Exposures: Clinical risk factors measured at baseline including age, LVEF, and NYHA heart failure class. Main Outcomes and Measures: Primary outcome of SAD, which is a composite of SAD and resuscitated ventricular fibrillation arrest. Results: The mean (SD) age of the cohort was 64 (11) years. During a median of 3.9 years, the cumulative incidence of SAD and non-SAD was 2.1% and 7.7%, respectively. Sudden and/or arrhythmic death was the most common mode of cardiovascular death accounting for 114 of 202 cardiac deaths (56%), although noncardiac death was the primary mode of death in this population. The 4-year cumulative incidence of SAD was lowest in those with an LVEF of more than 60% (1.0%) and highest among those with LVEF of 30% to 40% (4.9%) and class III/IV heart failure (5.1%); however, the cumulative incidence of non-SAD was similarly elevated in these latter high-risk subgroups. Patients with a moderately reduced LVEF (40%-49%) were more likely to die of SAD, whereas those with class II heart failure and advancing age were more likely to die of non-SAD. The proportion of deaths due to SAD varied widely, from 14% (18 of 131 deaths) in patients with NYHA II to 49% (37 of 76 deaths) in those younger than 60 years. Conclusions and Relevance: In a contemporary population of patients with coronary heart disease without severe systolic dysfunction, SAD accounts for a significant proportion of overall mortality. Moderately reduced LVEF, age, and NYHA class distinguished SAD and non-SAD, whereas other markers were equally associated with both modes of death. Absolute and proportional risk of SAD varied significantly across clinical subgroups, and both will need to be maximized in future risk stratification efforts.


Assuntos
Doença das Coronárias/complicações , Morte Súbita Cardíaca/epidemiologia , Medição de Risco/métodos , Função Ventricular Esquerda/fisiologia , Canadá/epidemiologia , Doença das Coronárias/mortalidade , Morte Súbita Cardíaca/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Sístole , Estados Unidos/epidemiologia , Disfunção Ventricular Esquerda
5.
JAMA Netw Open ; 1(8): e185708, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30646282

RESUMO

Importance: Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations. Objective: To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population. Design, Setting, and Participants: Using a prospective cohort design, baseline MED intake was assessed in 25 994 initially healthy US women in the Women's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018. Exposures: Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED. Main Outcomes and Measures: Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators. Results: Among 25 994 women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (P for trend < .001). The largest mediators of the CVD risk reduction of MED intake were biomarkers of inflammation (accounting for 29.2% of the MED-CVD association), glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%), followed by blood pressure (26.6%), traditional lipids (26.0%), high-density lipoprotein measures (24.0%) or very low-density lipoprotein measures (20.8%), with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%). Conclusions and Relevance: In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel.


Assuntos
Doenças Cardiovasculares , Dieta Mediterrânea , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
6.
Heart ; 103(24): 1954-1961, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28988211

RESUMO

OBJECTIVE: Limited data exist on the association between menopause and atrial fibrillation (AF). We sought to examine the relationship between menopausal age, postmenopausal hormone therapy (PHT) use and incident AF. METHODS: The Women's Health Study (WHS) enrolled 39 876 female health professionals between 1992 and 1995. We prospectively examined 30 034 women in WHS using Cox proportional-hazard models. Participants were free of cardiovascular disease and AF at baseline and had not undergone hysterectomy without bilateral oophorectomy prior to menopause. Incident AF was confirmed by medical record review. RESULTS: At baseline, median age was 53 years (IQR 49-60), median menopausal age was 50 years (IQR 46-52) and 14 415 (48.0%) had prior PHT use. Over a median follow-up of 20.5 years, 1350 AF events occurred. In multivariable analysis, relative hazards for AF were lower among women with younger age at menopause but did not differ significantly from women with the oldest menopausal age (<45: HR 0.82, 95% CI 0.67 to 1.02; 45-49: HR 0.90, 95% CI 0.74 to 1.08; 50-54: HR 0.89, 95% CI 0.75 to 1.06; >54 years: referent). Use of oestrogen-alone PHT, but not oestrogen and progesterone, was independently associated with AF risk (HR 1.22; 95% CI 1.02 to 1.45 vs HR 1.04; 95% CI 0.86 to 1.26). This relationship was not attenuated by intermediary cardiovascular events. CONCLUSIONS: In this large prospective study, menopausal age was not significantly related to incident AF, while use of oestrogen monotherapy was associated with increased AF risk. Our findings suggest a pathophysiological link between unopposed oestrogen exposure and AF in women. CLINICAL TRIAL REGISTRATION: NCT000000479; Post-results.


Assuntos
Fibrilação Atrial/epidemiologia , Terapia de Reposição de Estrogênios/efeitos adversos , Menopausa , Pós-Menopausa , Progesterona/uso terapêutico , Fatores Etários , Fibrilação Atrial/diagnóstico , Feminino , Humanos , Incidência , Modelos Lineares , Pessoa de Meia-Idade , Análise Multivariada , Progesterona/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
7.
JACC Heart Fail ; 5(8): 552-560, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28624486

RESUMO

OBJECTIVES: This study sought to identify modifiable risk factors and estimate the impact of risk factor modification on heart failure (HF) risk in women with new-onset atrial fibrillation (AF). BACKGROUND: Incident HF is the most common nonfatal event in patients with AF, although strategies for HF prevention are lacking. METHODS: We assessed 34,736 participants in the Women's Health Study who were free of prevalent cardiovascular disease at baseline. Cox models with time-varying assessment of risk factors after AF diagnosis were used to identify significant modifiable risk factors for incident HF. RESULTS: Over a median follow-up of 20.6 years, 1,495 women developed AF without prevalent HF. In multivariable models, new-onset AF was associated with an increased risk of HF (hazard ratio [HR]: 9.03; 95% confidence interval [CI]: 7.52 to 10.85). Once women with AF developed HF, all-cause (HR: 1.83; 95% CI: 1.37 to 2.45) and cardiovascular mortality (HR: 2.87; 95% CI: 1.70 to 4.85) increased. In time-updated, multivariable models accounting for changes in risk factors after AF diagnosis, systolic blood pressure >120 mm Hg, body mass index ≥30 kg/m2, current tobacco use, and diabetes mellitus were each associated with incident HF. The combination of these 4 modifiable risk factors accounted for an estimated 62% (95% CI: 23% to 83%) of the population-attributable risk of HF. Compared with women with 3 or 4 risk factors, those who maintained or achieved optimal risk factor control had a progressive decreased risk of HF (HR for 2 risk factors: 0.60; 95% CI: 0.37 to 0.95; 1 risk factor: 0.40; 95% CI: 0.25 to 0.63; and 0 risk factors: 0.14; 95% CI: 0.07 to 0.29). CONCLUSIONS: In women with new-onset AF, modifiable risk factors including obesity, hypertension, smoking, and diabetes accounted for the majority of the population risk of HF. Optimal levels of modifiable risk factors were associated with decreased HF risk. Prospective assessment of risk factor modification at the time of AF diagnosis may warrant future investigation.


Assuntos
Fibrilação Atrial/complicações , Insuficiência Cardíaca/etiologia , Idoso , Fibrilação Atrial/mortalidade , Índice de Massa Corporal , Estudos de Coortes , Complicações do Diabetes/complicações , Complicações do Diabetes/mortalidade , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Hipertensão/complicações , Hipertensão/mortalidade , Incidência , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/mortalidade , Prognóstico , Fatores de Risco , Fumar/mortalidade , Estados Unidos/epidemiologia
8.
PLoS One ; 11(11): e0165615, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27902713

RESUMO

BACKGROUND: Acute phase proteins highlight the dynamic interaction between inflammation and oncogenesis. GlycA, a novel nuclear magnetic resonance (NMR) inflammatory marker that identifies primarily circulating N-acetyl glycan groups attached to acute phase proteins, may be a future CRC risk biomarker. METHODS: We examined the association between GlycA and incident CRC and mortality in two prospective cohorts (N = 34,320); Discovery cohort: 27,495 participants from Women's Health Study (WHS); Replication cohort: 6,784 participants from Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable Cox models were adjusted for clinical risk factors and compared GlycA to acute phase proteins (high-sensitivity C-reactive protein [hsCRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]). RESULTS: In WHS (median follow-up 19 years, 337 cases, 103 deaths), adjusted HRs (95% CIs) per SD increment of GlycA for CRC incidence and mortality were 1.19 (1.06-1.35; p = 0.004) and 1.24 (1.00-1.55; p = 0.05), respectively. We replicated findings in MESA (median follow-up 11 years, 70 cases, 23 deaths); HRs (95% CIs) per SD of GlycA for CRC incidence and mortality were 1.32 (1.06-1.65; p = 0.01) and 1.54 (1.06-2.23; p = 0.02), respectively, adjusting for age, sex, and race. Pooled analysis, adjusted HR (95% CI) per SD of GlycA for CRC incidence and mortality was 1.26 (1.15-1.39; p = 1 x 10-6). Other acute phase proteins (hsCRP, fibrinogen, and sICAM-1) had weaker or no association with CRC incidence, while only fibrinogen and GlycA were associated with CRC mortality. CONCLUSIONS: The clinical utility of GlycA to personalize CRC therapies or prevention warrants further study. TRIAL REGISTRATION: ClinicalTrials.gov: WHS NCT00000479, MESA NCT00005487.


Assuntos
Biomarcadores/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/mortalidade , Glicoproteínas/sangue , Polissacarídeos/sangue , Proteínas da Fase Aguda/análise , Idoso , Proteína C-Reativa/análise , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologia
9.
Am J Clin Nutr ; 103(6): 1397-407, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27099252

RESUMO

BACKGROUND: Lipid biomarkers, such as HDL-cholesterol concentrations, have been shown to have positive, inverse, and null associations with total, breast, and colorectal cancer risks. Studies of novel lipid biomarkers, such as apolipoprotein A-I (apo A-I) and apolipoprotein B-100 (apo B-100), and cancer risk have been sparse, to our knowledge. OBJECTIVES: We evaluated the prospective association of total, breast, colorectal, and lung cancers and cancer mortality with circulating lipid biomarkers in 15,602 female health professionals in the Women's Health Study (aged ≥45 y, free of cardiovascular disease and cancer, and without hormone replacement therapy or lipid-lowering medications at baseline). DESIGN: Cox regression models estimated HRs of cancer endpoints (19 y median follow-up) across quartiles 1 (reference) to 4 of each lipid biomarker after adjustment for cancer risk factors. RESULTS: Confirmed cases included 2163 incident cancer cases (864 breast, 198 colorectal, and 190 lung cancers) and 647 cancer deaths. Total cancer risk was significantly lower in the highest quartile of apo A-I (adjusted HR: 0.79; 95% CI: 0.70, 0.90; P-trend = 0.0008) and HDL cholesterol (HR: 0.85; 95% CI: 0.75, 0.97; P-trend = 0.01). For site-specific cancers, significant associations included colorectal cancer risk with HDL cholesterol (HR: 0.63; 95% CI; 0.41, 0.98; P-trend = 0.03), triglycerides (HR: 1.86; 95% CI: 1.17, 2.97; P-trend = 0.02), and apo B-100 (HR: 1.60; 95% CI: 1.03, 2.49; P-trend = 0.006) and lung cancer risk with HDL cholesterol (HR: 0.59; 95% CI: 0.38, 0.93; P-trend = 0.01). LDL cholesterol was not significantly associated with risk of total cancer or any site-specific cancers. In time-dependent models that were adjusted for the use of a lipid-lowering medication after baseline, these associations remained. CONCLUSIONS: Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.


Assuntos
Biomarcadores/sangue , Lipídeos , Neoplasias/epidemiologia , Saúde da Mulher , Idoso , Apolipoproteína A-I/sangue , Apolipoproteína B-100/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/epidemiologia , Pessoa de Meia-Idade , Neoplasias/mortalidade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Comportamento de Redução do Risco , Triglicerídeos/sangue
10.
Circ Res ; 118(7): 1106-15, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26951635

RESUMO

RATIONALE: Circulating glycoprotein N-acetyl glucosamine residues have recently been associated with incident cardiovascular disease and diabetes mellitus. OBJECTIVE: Using a plasma glycan biosignature (GlycA) to identify circulating N-acetyl glycan groups, we examined the longitudinal association between GlycA and mortality among initially healthy individuals. METHODS AND RESULTS: We quantified GlycA by 400 MHz (1)H nuclear magnetic resonance spectroscopy in 27,524 participants in the Women's Health Study (NCT00000479). The primary outcome was all-cause mortality. We replicated the findings in an independent cohort of 12,527 individuals in the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681). We also undertook secondary examination of cardiovascular disease and cancer mortality in the Women's Health Study. In the Women's Health Study, during 524,515 person-years of follow-up (median, 20.5 years), there were 3523 deaths. Risk factor-adjusted multivariable Cox proportional hazard ratio (95% confidence interval) per SD increment in GlycA for all-cause mortality was significantly increased at 5 years (1.21 [1.06-1.40]) and during maximal follow-up (1.14 [1.09-1.16]). Similar risk for all-cause mortality was observed in the replication cohort (1.33 [1.21-1.45]). In the Women's Health Study, risk of cardiovascular disease mortality was increased at 5 years (1.43 [1.05-1.95]) and during maximal follow-up (1.15 [1.04-1.26]) and of cancer mortality at 5 years (1.23 [1.02-1.47]) and during maximal follow-up (1.08 [1.01-1.16]). Examination of correlations and mortality associations adjusted for high-sensitivity C-reactive protein, fibrinogen, and intercellular adhesion molecule-1, suggested that GlycA reflects summative risk related to multiple pathways of systemic inflammation. CONCLUSIONS: Among initially healthy individuals, elevated baseline circulating glycoprotein N-acetyl methyl groups were associated with longitudinal risk of all-cause, cardiovascular, and cancer mortality.


Assuntos
Acetilgalactosamina/sangue , Acetilglucosamina/sangue , Glicoproteínas/sangue , Mortalidade , Polissacarídeos/sangue , Proteínas da Fase Aguda/análise , Idoso , Biomarcadores , Proteínas Sanguíneas/análise , Proteína C-Reativa/análise , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Seguimentos , Glicoproteínas/química , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/sangue , Estimativa de Kaplan-Meier , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Ressonância Magnética Nuclear Biomolecular , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Estudos Retrospectivos , Risco
11.
J Nutr ; 145(9): 2092-101, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26180251

RESUMO

BACKGROUND: Dietary fats have effects on biological pathways that may influence the development and maintenance of atrial fibrillation (AF). However, associations between n-3 (ω-3) polyunsaturated fatty acids and AF are inconsistent, and data on other dietary fats and AF risk are sparse. OBJECTIVES: We examined the association between dietary fatty acid (FA) subclasses and risk of incident AF and explored whether these associations differed for sustained and paroxysmal AF. METHODS: We conducted a prospective cohort study in 33,665 women ≥45 y old without cardiovascular disease (CVD) and AF at baseline in 1993. Fat intake was estimated from food frequency questionnaires at baseline and in 2004. Incident AF was confirmed by medical records through October 2013. AF patterns were classified according to the most sustained form of AF within 2 y of diagnosis. Cox proportional hazards models with the use of a competing risk model approach estimated the RR. RESULTS: Over 19.2 y, 1441 cases of incident AF (929 paroxysmal and 467 persistent/chronic) were confirmed. Intakes of total fat and FA subclasses were not associated with risk of AF. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were differentially associated with AF patterns. The RR for a 5% increment of energy from SFAs was 1.47 (95% CI: 1.04, 2.09) for persistent/chronic and 0.85 (95% CI: 0.66, 1.08) for paroxysmal AF (P-difference = 0.01). For MUFAs, the RR for a 5% increment was 0.67 (95% CI: 0.46, 0.98) for persistent/chronic and 1.03 (95% CI: 0.78, 1.34) for paroxysmal AF, although the difference between patterns was not significant (P-difference = 0.07). CONCLUSIONS: Dietary fat was not associated with risk of incident AF in women without established CVD or AF. High SFA and low MUFA intakes were associated with greater risk of persistent or chronic, but not paroxysmal, AF. Improving dietary fat quality may play a role in the prevention of sustained forms of AF. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.


Assuntos
Fibrilação Atrial/epidemiologia , Gorduras na Dieta/administração & dosagem , Fibrilação Atrial/classificação , Ácidos Graxos/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
12.
Ann Intern Med ; 159(2): 77-85, 2013 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-23856681

RESUMO

BACKGROUND: Recent evidence suggests that daily aspirin use decreases cancer risk, particularly for colorectal cancer, but evidence for alternate-day use is scant. OBJECTIVE: To examine the association between long-term, alternate-day, low-dose aspirin and cancer in healthy women. DESIGN: Observational follow-up of a randomized trial. SETTING: Female health professionals. PARTICIPANTS: 39,876 women aged 45 years or older in the Women's Health Study (ClinicalTrials.gov: NCT00000479), 33 682 of whom continued observational follow-up. INTERVENTION: 100 mg of alternate-day aspirin or placebo through March 2004, with a median 10-year follow-up. Posttrial follow-up continued through March 2012. MEASUREMENTS: Cancer incidence. RESULTS: A total of 5071 cancer cases (including 2070 breast, 451 colorectal, and 431 lung cancer cases) and 1391 cancer deaths were confirmed. Over the entire follow-up, aspirin had no association with total (hazard ratio [HR], 0.97 [95% CI, 0.92 to 1.03]; P = 0.31), breast (HR, 0.98 [CI, 0.90 to 1.07]; P = 0.65), or lung (HR, 1.04 [CI, 0.86 to 1.26]; P = 0.67) cancer. Colorectal cancer was reduced in the aspirin group (HR, 0.80 [CI, 0.67 to 0.97]; P = 0.021), primarily for proximal colon cancer (HR, 0.73 [CI, 0.55 to 0.95]; P = 0.022). The difference emerged after 10 years, with a posttrial reduction of 42% (HR, 0.58 [CI, 0.42 to 0.80]; P < 0.001). There was no extended effect on cancer deaths or colorectal polyps. More gastrointestinal bleeding (HR, 1.14 [CI, 1.06 to 1.22]; P < 0.001) and peptic ulcers (HR, 1.17 [CI, 1.09 to 1.27]; P < 0.001) occurred in the aspirin group. LIMITATIONS: Not all women received extended follow-up, and posttrial ascertainment bias cannot be ruled out. Gastrointestinal bleeding, peptic ulcers, and polyps were self-reported during extended follow-up. CONCLUSION: Long-term use of alternate-day, low-dose aspirin may reduce risk for colorectal cancer in healthy women.


Assuntos
Aspirina/administração & dosagem , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Idoso , Aspirina/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Esquema de Medicação , Feminino , Seguimentos , Hemorragia Gastrointestinal/etiologia , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/prevenção & controle , Pessoa de Meia-Idade , Metástase Neoplásica , Inibidores da Agregação de Plaquetas/efeitos adversos
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