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1.
Stroke ; 51(10): 3156-3168, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32897811

RESUMO

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.


Assuntos
Aterosclerose/epidemiologia , Infecções/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , Aterosclerose/imunologia , Aterosclerose/fisiopatologia , Bacteriemia/epidemiologia , Bacteriemia/imunologia , Bacteriemia/fisiopatologia , Betacoronavirus , Doença Crônica , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/fisiopatologia , Endotélio/fisiopatologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Infecções/imunologia , Infecções/fisiopatologia , Inflamação/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/fisiopatologia , Pandemias , Ativação Plaquetária , Agregação Plaquetária , Pneumonia/epidemiologia , Pneumonia/imunologia , Pneumonia/fisiopatologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/imunologia , Trombose/epidemiologia , Trombose/imunologia , Infecção pelo Vírus da Varicela-Zoster/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/imunologia , Infecção pelo Vírus da Varicela-Zoster/fisiopatologia
2.
PLoS Med ; 17(8): e1003280, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32845900

RESUMO

BACKGROUND: Experimental and observational research has suggested the potential for increased type 2 diabetes (T2D) risk among populations taking statins for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, few studies have directly compared statin-associated benefits and harms or examined heterogeneity by population subgroups or assumed treatment effect. Thus, we compared ASCVD risk reduction and T2D incidence increases across 3 statin treatment guidelines or recommendations among adults without a history of ASCVD or T2D who were eligible for statin treatment initiation. METHODS AND FINDINGS: Simulations were conducted using Markov models that integrated data from contemporary population-based studies of non-Hispanic African American and white adults aged 40-75 years with published meta-analyses. Statin treatment eligibility was determined by predicted 10-year ASCVD risk (5%, 7.5%, or 10%). We calculated the number needed to treat (NNT) to prevent one ASCVD event and the number needed to harm (NNH) to incur one incident case of T2D. The likelihood to be helped or harmed (LHH) was calculated as ratio of NNH to NNT. Heterogeneity in statin-associated benefit was examined by sex, age, and statin-associated T2D relative risk (RR) (range: 1.11-1.55). A total of 61,125,042 U.S. adults (58.5% female; 89.4% white; mean age = 54.7 years) composed our primary prevention population, among whom 13-28 million adults were eligible for statin initiation. Overall, the number of ASCVD events prevented was at least twice as large as the number of incident cases of T2D incurred (LHH range: 2.26-2.90). However, the number of T2D cases incurred surpassed the number of ASCVD events prevented when higher statin-associated T2D RRs were assumed (LHH range: 0.72-0.94). In addition, females (LHH range: 1.74-2.40) and adults aged 40-50 years (LHH range: 1.00-1.14) received lower absolute benefits of statin treatment compared with males (LHH range: 2.55-3.00) and adults aged 70-75 years (LHH range: 3.95-3.96). Projected differences in LHH by age and sex became more pronounced as statin-associated T2D RR increased, with a majority of scenarios projecting LHHs < 1 for females and adults aged 40-50 years. This study's primary limitation was uncertainty in estimates of statin-associated T2D risk, highlighting areas in which additional clinical and public health research is needed. CONCLUSIONS: Our projections suggest that females and younger adult populations shoulder the highest relative burden of statin-associated T2D risk.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Cadeias de Markov , Guias de Prática Clínica como Assunto/normas , Adulto , Idoso , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto/métodos , Estudos Observacionais como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Resultado do Tratamento
3.
Ecotoxicol Environ Saf ; 204: 111039, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32738627

RESUMO

PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.


Assuntos
Aterosclerose/epidemiologia , Cádmio/urina , Espessura Intima-Media Carotídea , Metilação de DNA , Poluentes Ambientais/urina , Chumbo/urina , Adolescente , Adulto , Aterosclerose/induzido quimicamente , Biomarcadores , Estudos Transversais , Feminino , Humanos , Masculino , Taiwan/epidemiologia , Adulto Jovem
4.
Ecotoxicol Environ Saf ; 204: 111036, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32784013

RESUMO

Human exposure to methylmercury (MeHg) due to contaminated fish intake as part of a high-fat (HFD), high-carbohydrate diets is a reality today for many populations. HFD is associated with hypertension and hyperlipidemia, primary cardiovascular disease (CVD) risk factors. Some studies suggest that MeHg induces those risk factors. We evaluated the effect of MeHg exposure in mice fed with HFD or control diet for eight weeks. In the last experimental 15 days, the half group received a MeHg solution (20 mg/L) replacing water. Blood pressure (BP), heart rate, lipoprotein concentrations, and paraoxonase activity were evaluated. Liver cholesterol, triacylglycerol, and IBA-1+ cells, as well as transcriptional levels of genes related to lipid metabolism and inflammatory response, were also assessed. HFD and both MeHg groups presented increased BP and total cholesterol (TC). In the liver, HFD but not MeHg was related to an increase in TC. Also, MeHg intoxication reduced paraoxonase activity regardless of diet. MeHg intoxication and HFD increased steatosis and the number of IBA-1+ cells and modified some gene transcripts associated with lipid metabolism. In conclusion, we demonstrated that MeHg effects on CVD risk factors resemble those caused by HFD.


Assuntos
Pressão Arterial/efeitos dos fármacos , Aterosclerose/epidemiologia , Dieta Hiperlipídica/efeitos adversos , Poluentes Ambientais/efeitos adversos , Fígado/efeitos dos fármacos , Compostos de Metilmercúrio/efeitos adversos , Estado Nutricional , Animais , Aterosclerose/induzido quimicamente , Fígado Gorduroso/metabolismo , Feminino , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Lipoproteínas/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Risco
5.
BMJ ; 370: m2297, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669282

RESUMO

OBJECTIVE: To evaluate the associations between prediabetes and the risk of all cause mortality and incident cardiovascular disease in the general population and in patients with a history of atherosclerotic cardiovascular disease. DESIGN: Updated meta-analysis. DATA SOURCES: Electronic databases (PubMed, Embase, and Google Scholar) up to 25 April 2020. REVIEW METHODS: Prospective cohort studies or post hoc analysis of clinical trials were included for analysis if they reported adjusted relative risks, odds ratios, or hazard ratios of all cause mortality or cardiovascular disease for prediabetes compared with normoglycaemia. Data were extracted independently by two investigators. Random effects models were used to calculate the relative risks and 95% confidence intervals. The primary outcomes were all cause mortality and composite cardiovascular disease. The secondary outcomes were the risk of coronary heart disease and stroke. RESULTS: A total of 129 studies were included, involving 10 069 955 individuals for analysis. In the general population, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.13, 95% confidence interval 1.10 to 1.17), composite cardiovascular disease (1.15, 1.11 to 1.18), coronary heart disease (1.16, 1.11 to 1.21), and stroke (1.14, 1.08 to 1.20) in a median follow-up time of 9.8 years. Compared with normoglycaemia, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 7.36 (95% confidence interval 9.59 to 12.51), 8.75 (6.41 to 10.49), 6.59 (4.53 to 8.65), and 3.68 (2.10 to 5.26) per 10 000 person years, respectively. Impaired glucose tolerance carried a higher risk of all cause mortality, coronary heart disease, and stroke than impaired fasting glucose. In patients with atherosclerotic cardiovascular disease, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.36, 95% confidence interval 1.21 to 1.54), composite cardiovascular disease (1.37, 1.23 to 1.53), and coronary heart disease (1.15, 1.02 to 1.29) in a median follow-up time of 3.2 years, but no difference was seen for the risk of stroke (1.05, 0.81 to 1.36). Compared with normoglycaemia, in patients with atherosclerotic cardiovascular disease, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 66.19 (95% confidence interval 38.60 to 99.25), 189.77 (117.97 to 271.84), 40.62 (5.42 to 78.53), and 8.54 (32.43 to 61.45) per 10 000 person years, respectively. No significant heterogeneity was found for the risk of all outcomes seen for the different definitions of prediabetes in patients with atherosclerotic cardiovascular disease (all P>0.10). CONCLUSIONS: Results indicated that prediabetes was associated with an increased risk of all cause mortality and cardiovascular disease in the general population and in patients with atherosclerotic cardiovascular disease. Screening and appropriate management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease.


Assuntos
Doenças Cardiovasculares/mortalidade , Doença das Coronárias/mortalidade , Estado Pré-Diabético/complicações , Acidente Vascular Cerebral/mortalidade , Idoso , Aterosclerose/complicações , Aterosclerose/epidemiologia , Aterosclerose/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Doença das Coronárias/epidemiologia , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Estado Pré-Diabético/epidemiologia , Risco , Fatores de Risco , Prevenção Secundária/métodos , Acidente Vascular Cerebral/epidemiologia
6.
PLoS One ; 15(7): e0236151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726349

RESUMO

BACKGROUND: Fuels burned in households for cooking cause indoor air pollution, exposing those who are cooking. Despite the mounting evidence of the effects of fuels use on health, few studies focus on the effect of cooking fuels have on carotid intima-media thickness (CIMT), a surrogate atherosclerosis biomarker in the early stages of pregnancy. This study aimed to examine the association between the use of cooking fuels and CIMT during early trimester of pregnancy among cooking women in Myanmar. METHODOLOGY: In this cross-sectional study, a part of an ongoing birth cohort analysis, a total of 192 cooking pregnant women over 18 years with gestational weeks less than 18 were recruited from 15 rural health centers in Nay Pyi Taw from September to November 2019. Sociodemographic data, residential data, and fuels use data were collected with semi-structured questionnaires in face-to-face interviews. Anthropometric, hemodynamic, blood lipids, and ultrasound CIMT measurements were performed under standard protocols. Multiple linear regression was modeled to explore associations. RESULTS: The study included 70 firewood fuel users, 26 charcoal fuel users, and 96 electricity fuel users. Following adjustments for potential confounding factors, firewood use was significantly associated with the increase of all CIMT analyzed. Importantly, a greater increase of mean CIMT of the right common carotid artery (RCCA; ß = 0.033 mm; 95%CI: 0.006, 0.058; P<0.05) had significant association with charcoal use compared to firewood use (ß = 0.029 mm; 95%CI: 0.010, 0.049; P<0.05). CONCLUSIONS: Our findings demonstrate that the indoor use of cooking fuels that cause indoor air pollution, such as firewood and charcoal, is a considerable risk factor for human health and is associated with increased CIMT, wherein charcoal use contributes to more increase of mean CIMT of the RCCA. Measures to prevent health risks related to the use of such fuels should be instituted early on during pregnancy.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Aterosclerose/epidemiologia , Espessura Intima-Media Carotídea , Culinária/métodos , Exposição por Inalação/efeitos adversos , Fumaça/efeitos adversos , Adulto , Aterosclerose/induzido quimicamente , Estudos Transversais , Características da Família , Feminino , Humanos , Incidência , Mianmar/epidemiologia , Gravidez , Fatores de Risco
7.
G Ital Cardiol (Rome) ; 21(7): 489-501, 2020 Jul.
Artigo em Italiano | MEDLINE | ID: mdl-32555564

RESUMO

Given the high prevalence of preexisting cardiovascular diseases and the increased incidence of adverse cardiovascular events in patients hospitalized for SARS-CoV-2 infection, the identification of optimal antithrombotic approaches in terms of risk/benefit ratio and outcome improvement appears crucial in this setting. In the present position paper we collected current evidence from the literature to provide practical recommendations on the management of antithrombotic therapies (antiplatelet and anticoagulant) in various clinical contexts prevalent during the SARS-CoV-2 outbreak: in-home management of oral anticoagulant therapy; interactions between drugs used in the SARS-CoV-2 infection and antithrombotic agents; in-hospital management of antithrombotic therapies; diagnosis, risk stratification and treatment of in-hospital thrombotic complications.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Fibrinolíticos/uso terapêutico , Pneumonia Viral/epidemiologia , Trombose/tratamento farmacológico , Aterosclerose/diagnóstico , Betacoronavirus , Comorbidade , Infecções por Coronavirus/diagnóstico , Medicina Baseada em Evidências , Feminino , Humanos , Incidência , Itália , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Guias de Prática Clínica como Assunto , Medição de Risco , Trombose/diagnóstico , Trombose/epidemiologia , Resultado do Tratamento
8.
PLoS Med ; 17(5): e1003115, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32379748

RESUMO

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association. METHODS AND FINDINGS: Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002-2008, mean age 65.2 years; 2009-2013, mean age 69.0 years; and 2014-2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34-2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9-54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [-10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [-10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity. CONCLUSIONS: In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.


Assuntos
Imunidade Adaptativa/imunologia , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Imunidade Inata/imunologia , Idoso , Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia
9.
PLoS One ; 15(5): e0232531, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357160

RESUMO

Atherosclerosis is a progressive inflammation in systemic vessels, and pesticide exposure has been emerging as its risk factor. This cross-sectional study investigated the association between pesticide exposure and the risk of atherosclerosis in a rural population in Korea using carotid intima-media thickness (CIMT). This study used dataset from the baseline survey of the Korea Farmers Cohort Study between November 2005 and January 2008, and the final analysis included 477 participants. Well-structured questionnaires were used to estimate pesticide exposure. CIMT ≥ 0.9 mm was established for carotid atherosclerosis. Multiple logistic regression analyses were undertaken to evaluate the association between pesticide exposure and atherosclerosis, adjusting demographic and health-related confounders. Even after adjustments, the increased risk of atherosclerosis was significantly associated with pesticide exposure, such as a lifetime history of farming (odds ratio [OR] 3.25 95% confidence interval [CI] 1.51-6.98), a history of using pesticide (OR 3.42 95% CI 1.63-7.16), using pesticide 10 times or more annually (OR 2.55 95% CI 1.21-5.39), and higher cumulative exposure index level (OR 3.63 95% CI 1.65-7.97). Further prospective studies are required to elucidate effects of pesticide exposure on the risk of atherosclerosis.


Assuntos
Aterosclerose/epidemiologia , Aterosclerose/etiologia , Praguicidas/toxicidade , Adulto , Idoso , Agricultura , Espessura Intima-Media Carotídea , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , População Rural , Inquéritos e Questionários
11.
Am J Cardiol ; 125(12): 1836-1844, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32331712

RESUMO

Atrial fibrillation (AF) is a common perioperative arrhythmia. However, its occurrence and implications remain poorly defined in the setting of noncardiac procedures. We sought to define the incidence, prevalence, and prognostic implications of AF among patients with atherosclerotic cardiovascular disease (ASCVD) undergoing noncardiac surgery. Using a previously validated approach that employed unique patient-linked variables in the New York State Inpatient Database from January 1, 2012, to December 31, 2014, the frequency of new-onset and pre-existing AF was determined in adults with ASCVD aged ≥18 years undergoing noncardiac surgery. The secondary outcomes were stroke within 1 month and all-cause mortality. Using multivariable logistic regression models, the factors and outcomes associated with new-onset AF after noncardiac surgery were assessed. Nine surgical subgroups of major noncardiac surgery served as exposure. A total of 184,775 patients were identified during the study period. Age ≥65, anemia, history of heart failure, valvular heart disease, and thoracic surgery were predictors of new-onset AF after noncardiac surgery. Among 3,806 patients (2.5%) developed new-onset AF and 31,603 (17.5%) patient had pre-existing AF. After multivariable-adjusted modeling, new-onset AF was associated with increased odds of stroke within 1 month (odds ratio: 1.31, 95% confidence interval: 1.12 to 1.53; p < 0.001)], mortality (odds ratio: 3.74; 95% confidence interval: 3.30 to 4.24; p < 0.001) and longer length of stay in the hospital (10 days; interquartile range: 6 to 16 days; p < 0.001). New-onset AF portends a poor prognosis in patients with ASCVD undergoing noncardiac surgeries. The risk profile of patients that develop new-onset AF differs across patient phenotypes and by surgical procedure.


Assuntos
Aterosclerose/epidemiologia , Fibrilação Atrial/epidemiologia , Procedimentos Cirúrgicos Eletivos , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Fenótipo , Prevalência , Prognóstico , Fatores de Risco
12.
Prog Cardiovasc Dis ; 63(3): 219-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277995

RESUMO

Elevated circulating concentrations of lipoprotein(a) [Lp(a)] is strongly associated with increased risk of atherosclerotic cardiovascular disease (CVD) and degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Everybody should have their Lp(a) concentration measured once in their lifetime. CVD risk is elevated when Lp(a) concentrations are high i.e. > 50 mg/dL (≥100 mmol/L). Extremely high Lp(a) levels >180 mg/dL (≥430 mmol/L) are associated with CVD risk similar to that conferred by familial hypercholesterolemia. Elevated Lp(a) level was previously treated with niacin, which exerts a potent Lp(a)-lowering effect. However, niacin is currently not recommended because, despite the improvement in lipid profile, no improvements on clinical outcomes have been observed. Furthermore, niacin use has been associated with severe adverse effects. Post hoc analyses of clinical trials with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have shown that these drugs exert clinical benefits by lowering Lp(a), independent of their potent reduction of low-density lipoprotein cholesterol (LDL-C). It is not yet known whether PCSK9 inhibitors will be of clinical use in patients with elevated Lp(a). Apheresis is a very effective approach to Lp(a) reduction, which reduces CVD risk but is invasive and time-consuming and is thus reserved for patients with very high Lp(a) levels and progressive CVD. Studies are ongoing on the practical application of genetic approaches to therapy, including antisense oligonucleotides against apolipoprotein(a) and small interfering RNA (siRNA) technology, to reduce the synthesis of Lp(a).


Assuntos
Estenose da Valva Aórtica/sangue , Valva Aórtica/patologia , Artérias/metabolismo , Aterosclerose/sangue , Calcinose/sangue , Lipoproteína(a)/sangue , Placa Aterosclerótica , Animais , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/terapia , Artérias/patologia , Aterosclerose/epidemiologia , Aterosclerose/patologia , Aterosclerose/terapia , Biomarcadores/sangue , Calcinose/epidemiologia , Calcinose/patologia , Calcinose/terapia , Humanos , Lipoproteína(a)/química , Prognóstico , Fatores de Risco , Regulação para Cima
13.
Am Heart J ; 224: 65-76, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32335402

RESUMO

BACKGROUND: Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES: Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS: In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS: Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS: In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT: In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.


Assuntos
Androgênios/deficiência , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , Síndrome Metabólica/complicações , Medição de Risco/métodos , Testosterona/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Androgênios/sangue , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Método Duplo-Cego , Seguimentos , Humanos , Incidência , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
14.
Stroke ; 51(5): 1546-1554, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32312223

RESUMO

Background and Purpose- The PCSK9 (proprotein convertase subtilisin-kexin type 9) monoclonal antibody evolocumab lowered LDL (low-density lipoprotein) cholesterol by 59% to 0.8 (0.5-1.2) mmol/L and significantly reduced major vascular events in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk). Herein, we report the results of a prespecified analysis of cerebrovascular events in the overall trial population and in patients stratified by prior stroke. Methods- FOURIER was a randomized, double-blind trial comparing evolocumab versus placebo in patients with established atherosclerosis, additional risk factors, and LDL cholesterol levels ≥1.8 (or non-HDL [high-density lipoprotein] ≥2.6 mmol/L) on statin therapy. The median follow-up was 2.2 years. We analyzed the efficacy of evolocumab to reduce overall stroke and stroke subtypes, as well as the primary cardiovascular composite end point by subgroups according to a history of stroke. Results- Among the 27 564 patients, 469 (1.7%) experienced a total of 503 strokes of which 421 (84%) were ischemic. Prior ischemic stroke, diabetes mellitus, elevated CRP (C-reactive protein), history of heart failure, older age, nonwhite race, peripheral arterial disease, and renal insufficiency were independent predictors of stroke. Evolocumab significantly reduced all stroke (1.5% versus 1.9%; hazard ratio, 0.79 [95% CI, 0.66-0.95]; P=0.01) and ischemic stroke (1.2% versus 1.6%; hazard ratio, 0.75 [95% CI, 0.62-0.92]; P=0.005), with no difference in hemorrhagic stroke (0.21% versus 0.18%; hazard ratio, 1.16 [95% CI, 0.68-1.98]; P=0.59). These findings were consistent across subgroups, including among the 5337 patients (19%) with prior ischemic stroke in whom the hazard ratios (95% CIs) were 0.85 (0.72-1.00) for the cardiovascular composite, 0.90 (0.68-1.19) for all stroke, and 0.92 (0.68-1.25) for ischemic stroke (P interactions, 0.91, 0.22, and 0.09, respectively, compared with patients without a prior ischemic stroke). Conclusions- Inhibition of PCSK9 with evolocumab added to statin in patients with established atherosclerosis reduced ischemic stroke and cardiovascular events in the total population and in key subgroups, including those with prior ischemic stroke. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01764633.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Doença Arterial Periférica/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aterosclerose/epidemiologia , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
15.
BMC Med Genet ; 21(1): 62, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32220223

RESUMO

BACKGROUND: To examine the association between lipoprotein(a) (Lp(a)) levels, LPA (rs10455872 and rs3798220) and IL1F9 (rs13415097) single nucleotide polymorphisms (SNPs) with coronary artery calcification (CAC), an important predictor for coronary artery disease (CAD). METHODS: We used data from 3799 (mean age ± SD: 59.0 ± 7.7 years, 47.1% men) Heinz Nixdorf Recall study participants. We applied linear regression models to explore the relation between the log-transformed Lp(a) levels and LPA and IL1F9 SNPs with loge (CAC + 1). The association between the SNPs and log-transformed Lp(a) levels was further assessed using linear regression. The models were adjusted for age and sex (Model 1) and additionally for Lp(a) levels (Model 2). RESULTS: We observed a statistically significant association between log-transformed Lp(a) levels and CAC (Model 1: beta per log-unit increase in Lp(a) levels = 0.11; 95% confidence interval [95% CI] [0.04; 0.18], p = 0.002). Furthermore, the LPA SNP rs10455872 showed a statistically significant association with CAC (Model 1: beta per allele = 0.37 [0.14; 0.61], p = 0.002). The association between rs10455872 and CAC was attenuated after adjustment for Lp(a) levels (Model 2: beta per allele = 0.26 [- 0.01; 0.53], p = 0.06). Both LPA SNPs also showed a statistically significant association with Lp(a) levels (Model 1: betars10455872 per allele: 1.56 [1.46; 1.65], p < 0.0001 and betars3798220 per allele: 1.51 [1.33; 1.69], p < 0.0001)). The Mendelian randomization analysis showed that Lp(a) is a causal risk factor for CAC (estimate per log-unit increase in Lp(a) levels (95% CI), p: 0.27 [0.11; 0.44], p = 0.001). The IL1F9 SNP did not show any statistically significant association with Lp(a) levels or with CAC. CONCLUSIONS: We provide evidence for the association of LPA rs10455872 with higher levels of Lp(a) and CAC in our study. The results of our study suggest that rs10455872, mediated by Lp(a) levels, might play a role in promoting the development of atherosclerosis leading to cardiovascular disease events.


Assuntos
Doença da Artéria Coronariana , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Polimorfismo de Nucleotídeo Único , Calcificação Vascular , Idoso , Alelos , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/genética , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Vasos Coronários/patologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular/sangue , Calcificação Vascular/epidemiologia , Calcificação Vascular/genética
16.
High Blood Press Cardiovasc Prev ; 27(3): 231-238, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32219668

RESUMO

INTRODUCTION: Age is traditionally considered a major cardiovascular (CV) risk factor, but its real weight in the absence of other modifiable risk factors is not clear. AIM: To compare the prevalence of subclinical carotid atherosclerosis, and its association with the main CV risk factors, between older adults and hypertensive adults. METHODS: Cross-sectional study on 210 consecutive patients: 70 older adults (age ≥ 80 years), and 140 hypertensive adults having at least another CV risk factor. Patients had no history of peripheral artery disease or major CV events. RESULTS: Mean age was 54.2 ± 7.2 years in hypertensive adults and 88.5 ± 5.5 years in older adults with a female prevalence in the latter group. Dyslipidemia and smoking were more prevalent in hypertensive adults, while chronic kidney disease was more prevalent in older adults. Prevalence of carotid plaques did not differ between hypertensive adults and older adults (48.2% vs 55.6%, respectively, p = 0.311). Age ≥ 80 years was not associated with a higher risk of carotid plaques even after adjusting for other risk factors (p = 0.204). Hypertension and dyslipidemia were the risk factors more strongly associated with carotid plaques in older adults and hypertensive adults, respectively. When older adults with hypertension were excluded from the analysis, prevalence of carotid plaques was significantly higher in hypertensive adults (p = 0.042). CONCLUSION: Hypertension and dyslipidemia are the major determinant of atherosclerosis regardless of age in our study. Our findings support the concept that aging is not necessarily synonymous with atherosclerosis and highlight the key role played by superimposed CV risk factors on arterial ''bad aging''.


Assuntos
Envelhecimento , Aterosclerose/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Adulto , Fatores Etários , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Aterosclerose/diagnóstico por imagem , Biomarcadores/sangue , Pressão Sanguínea , Doenças das Artérias Carótidas/diagnóstico por imagem , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Nível de Saúde , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Itália/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais
18.
BMC Public Health ; 20(1): 403, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32220240

RESUMO

BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVD) are on the rise in low and middle-income countries attributed to modern sedentary lifestyle and dietary habits. This has led to the need of assessment of the burden of at-risk population so that prevention measures can be developed. The objective of this study was to assess ten years risk assessment of ASCVD using Astro-CHARM and Pooled Cohort Equation (PCE) in a South Asian sub-population. METHODS: A total of 386 residents of all six districts of Karachi with no ASCVD were enrolled in the study through an exponential non-discriminative referral snowball sampling technique. The inclusion criteria consisted of age 40 years or above and either gender. Study participants were enrolled after obtaining informed written consent and those study participants who were found to have either congenital heart disease or valvular heart diseases or ischemic heart disease were excluded from the study based on initial screening. For the calculation of 10 years risk of ACVD based on Astro-CHARM and PCE, the variables were obtained including medical history and coronary artery calcium and C-reactive protein measurements. RESULTS: Mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the Astro-CHARM was 13.98 ± 8.01%, while mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the PCE was 22.26 ± 14.01%. Based on Astro-CHARM, 11.14% of the study participants were labeled as having high risk, while PCE estimated 20.73% of study participants as having high risk of ASCVD. CONCLUSION: Despite the fact that our findings showed substantial differences in ten-year risk of ASCVD between Astro-CHARM and PCE, both calculators can be used to develop a new population and specific risk estimators for this South Asian sub-population. Our study provides the first step towards developing a risk assessment guided decision-making protocol for primary prevention of ASCVD in this population.


Assuntos
Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Adulto , Ásia/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos
19.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32209700

RESUMO

BACKGROUND: The association of dietary fat distribution with markers of subclinical atherosclerosis during early life is unknown. We examined whether success in achieving the main target of an infancy-onset dietary intervention based on the distribution of dietary fat was associated with aortic and carotid intima-media thickness (IMT) and distensibility from childhood to young adulthood. METHODS: In the prospective randomized controlled Special Turku Coronary Risk Factor Intervention Project trial, personalized dietary counseling was given biannually to healthy children from infancy to young adulthood. The counseling was based on Nordic Nutrition Recommendations, with the main aim of improving the distribution of dietary fat in children's diets. IMT and distensibility of the abdominal aorta and common carotid artery were measured repeatedly at ages 11 (n = 439), 13 (n = 499), 15 (n = 506), 17 (n = 477), and 19 years (n = 429). The targeted distribution of dietary fat was defined as a ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids of <1:2 and as an intake of saturated fatty acids of <10% of energy intake. Participants who met ≥1 of these 2 criteria were defined to achieve the main intervention target. RESULTS: Individuals who achieved the main intervention target had lower aortic IMT (age- and sex-adjusted mean difference 10.4 µm; 95% confidence interval: 0.3 to 20.5 µm) and better aortic distensibility (0.13% per 10 mm Hg; 95% confidence interval: 0.00% to 0.26% per10 mm Hg) compared with their peers who did not meet the target. CONCLUSIONS: Achieving the main target of an infancy-onset dietary intervention, reflecting dietary guidelines, was favorably associated with aortic IMT and distensibility during the early life course. These data support the recommendation of favoring unsaturated fat to enhance arterial health.


Assuntos
Aterosclerose/prevenção & controle , Dieta com Restrição de Gorduras/métodos , Gorduras na Dieta/farmacologia , Ingestão de Energia/fisiologia , Adolescente , Aorta Torácica/diagnóstico por imagem , Aterosclerose/epidemiologia , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Criança , Aconselhamento , Progressão da Doença , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
20.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32209701

RESUMO

BACKGROUND: Elevated non-high-density lipoprotein cholesterol (HDL-C) levels are used to identify children at increased cardiovascular risk, but the use of non-HDL-C in childhood to predict atherosclerosis is unclear. We examined whether the National Heart, Lung, and Blood Institute classification of youth non-HDL-C status predicts high common carotid artery intima-media thickness in adulthood. METHODS: We analyzed data from 4 prospective cohorts among 4582 children aged 3 to 19 years who were remeasured as adults (mean follow-up of 26 years). Non-HDL-C status in youth and adulthood was classified according to cut points of the National Heart, Lung, and Blood Institute and the National Cholesterol Education Program Adult Treatment Panel III. High carotid intima-media thickness (cIMT) in adulthood was defined as at or above the study visit-, age-, sex-, race-, and cohort-specific 90th percentile of intima-media thickness. RESULTS: In a log-binomial regression analysis adjusted with age at baseline, sex, cohort, length of follow-up, baseline BMI, and systolic blood pressure, children with dyslipidemic non-HDL-C were at increased risk of high cIMT in adulthood (relative risk [RR], 1.29; 95% confidence interval [CI], 1.07-1.55). Compared with the persistent normal group, the persistent dyslipidemia group (RR, 1.80; 95% CI, 1.37-2.37) and incident dyslipidemia (normal to dyslipidemia) groups (RR, 1.45; 95% CI, 1.07-1.96) had increased risk of high cIMT in adulthood, but the risk was attenuated for the resolution (dyslipidemia to normal) group (RR, 1.17; 95% CI, 0.97-1.41). CONCLUSIONS: Dyslipidemic non-HDL-C levels predict youth at risk for developing high cIMT in adulthood. Those who resolve their non-HDL-C dyslipidemia by adulthood have normalized risk of developing high cIMT in adulthood.


Assuntos
Aterosclerose/sangue , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Colesterol/sangue , Previsões , Medição de Risco/métodos , Adolescente , Adulto , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Austrália/epidemiologia , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue , Estados Unidos/epidemiologia , Adulto Jovem
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