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1.
Prog Cardiovasc Dis ; 62(5): 414-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31669498

RESUMO

Familial hypercholesterolemia (FH) is a frequent genetic disorder characterized by elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) levels and early onset of atherosclerotic cardiovascular disease. FH is caused by mutations in genes that regulate LDL catabolism, mainly the LDL receptor (LDLR), apolipoprotein B (APOB) and gain of function of proprotein convertase subtilisin kexin type 9 (PCSK9). However, the phenotype may be encountered in individuals not carrying the latter monogenic defects, in approximately 20% of these effects of polygenes predominate, and in many individuals no molecular defects are encountered at all. These so-called FH phenocopy individuals have an elevated atherosclerotic cardiovascular disease risk in comparison with normolipidemic individuals but this risk is lower than in those with monogenic disease. Individuals with FH are exposed to elevated LDL-C levels since birth and this explains the high cardiovascular, mainly coronary heart disease, burden of these subjects. However, recent studies show that this risk is heterogenous and depends not only on high LDL-C levels but also on presence of previous cardiovascular disease, a monogenic cause, male sex, smoking, hypertension, diabetes, low HDL-cholesterol, obesity and elevated lipoprotein(a). This heterogeneity in risk can be captured by risk equations like one from the SAFEHEART cohort and by detection of subclinical coronary atherosclerosis. High dose high potency statins are the main stain for LDL-C lowering in FH, however, in most situations these medications are not powered enough to reduce cholesterol to adequate levels. Ezetimibe and PCSK9 inhibitors should also be used in order to better treat LDL-C in FH patients.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , Aterosclerose/epidemiologia , Aterosclerose/genética , Biomarcadores/sangue , Ezetimiba/uso terapêutico , Predisposição Genética para Doença , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Fenótipo , Pró-Proteína Convertase 9/antagonistas & inibidores , Pró-Proteína Convertase 9/metabolismo , Medição de Risco , Fatores de Risco , Inibidores de Serino Proteinase/uso terapêutico , Resultado do Tratamento
3.
Nutr Metab Cardiovasc Dis ; 29(10): 1068-1076, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378630

RESUMO

BACKGROUND AND AIM: Heterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical atherosclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences. METHODS AND RESULTS: 154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid profiles and HeHF history were obtained from patients' files in order to calculate total CB. Atherosclerotic burden was defined by the presence of CACs > 0 or by the presence of carotid or femoral plaque. Study population was stratified according to gender. The prevalence of CAC, carotid and femoral atherosclerosis was of 62%, 55% and 56%, respectively. Coronary district was the least involved in women, who had a higher prevalence in carotid atherosclerosis. When two vascular districts were affected, women had an increased prevalence of femoral and carotid atherosclerosis whereas men had a higher prevalence of coronary and femoral atherosclerosis. CB correlated to the presence of atherosclerosis in any of the three vascular districts with a significant increasing trend depending on the number of affected areas. CONCLUSIONS: A polyvascular atherosclerotic burden is found in asymptomatic HeFH patients. Gender differences in the territory distribution were observed. The early and lasting exposure to high cholesterol, as expressed by CB, is a major determinant of atherosclerotic burden.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Colesterol/sangue , Doença da Artéria Coronariana/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Doença Arterial Periférica/epidemiologia , Adulto , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Feminino , Artéria Femoral/diagnóstico por imagem , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico por imagem , Fenótipo , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
4.
Clin Cardiol ; 42(10): 988-994, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436336

RESUMO

BACKGROUND: Previous studies have observed that high level of lipoprotein (a) [Lp(a)] was common in the phenotypic familial hypercholesterolemia (FH) and may explain part of the clinical diagnosis of FH. HYPOTHESIS: We aim to develop a modified model including Lp(a) and compare its diagnostic performance with Dutch Lipid Clinic Network (DLCN) criteria. METHODS: Data of 10 449 individuals were utilized for the model establishment (7806 for derivation and 2643 for validation) from January 2011 to March 2018. The novel score model was modified on the basis of DLCN. Furthermore, 718 patients were screened for LDLR, APOB, and PCSK9 gene mutations. RESULTS: The novel modified model consisted of untreated low-density lipoprotein cholesterol (LDL-C) level, Lp(a), personal premature coronary heart disease (CHD), tendon xanthomas and family history of CHD and/or hypercholesterolemia. It has shown high discrimination (area under curve [AUC] 0.991, 95% confidence interval [CI[ 0.988-0.994, P < .001) for distinguishing clinical FH from non-FH diagnosed using DLCN. Furthermore, a concordance analysis was performed to compare the modified model with DLCN and it showed a good agreement with DLCN (κ = 0.765). External validation of the novel model also showed good accordance (κ = 0.700). Further genetic analysis showed that the agreements between the new model and mutation improved a little compared to that between DLCN and mutation. CONCLUSIONS: The novel modified model, including Lp(a), could provide new insights into FH diagnosis in Chinese population with more concerns on the patients with high level of Lp(a).


Assuntos
Algoritmos , Hiperlipoproteinemia Tipo II/diagnóstico , Lipoproteína(a)/sangue , Biomarcadores/sangue , China/epidemiologia , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Indian Heart J ; 71(2): 118-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280822

RESUMO

AIMS: The prevalence of premature coronary artery disease (CAD) in India is two to three times more than other ethnic groups. Untreated heterozygous familial hypercholesterolemia (FH) is one of the important causes for premature CAD. As the age advances, these patients without treatment have 100 times increased risk of cardiovascular (CV) mortality resulting from myocardial infarction (MI). Recent evidence suggests that one in 250 individuals may be affected by FH (nearly 40 million people globally). It is indicated that the true global prevalence of FH is underestimated. The true prevalence of FH in India remains unknown. METHODS: A total of 635 patients with premature CAD were assessed for FH using the Dutch Lipid Clinical Network (DLCN) criteria. Based on scores, patients were diagnosed as definite, probable, possible, or no FH. Other CV risk factors known to cause CAD such as smoking, diabetes mellitus, and hypertension were also recorded. RESULTS: Of total 635 patients, 25 (4%) were diagnosed as definite, 70 (11%) as probable, 238 (37%) as possible, and 302 (48%) without FH, suggesting the prevalence of potential (definite + probable) FH of about 15% in the North Indian population. FH is more common in younger patients, and they have lesser incidence of common CV risk factors such as diabetes, hypertension, and smoking than the younger MI patients without FH (26.32% vs.42.59%; 17.89% vs.29.44%; 22.11% vs.40.74%). CONCLUSION: FH prevalence is high among patients with premature CAD admitted to a cardiac unit. To detect patients with FH, routine screening with simple criteria such as family history of premature CAD combined with hypercholesterolemia, and a DLCN criteria score >5 may be effectively used.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Adulto , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Centros de Atenção Terciária
6.
BMC Public Health ; 19(1): 837, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248412

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) is a common monogenic disease, while studies about the epidemiology for the general population in China was scarce. Aim of the study was to estimate the prevalence of FH and explore related factors by the Chinese modified Dutch Lipid Clinic Network (DLCN) definition. METHODS: A total of 39,205 participants (15,463 males and 23,742 females) aged 18-79 years old were enrolled from the Henan Rural Cohort Study. FH was defined by the Chinese modified DLCN definition, and score > 5 was classified as FH. Logistic regression analysis was used to calculate the odds ratio and 95% confidence interval. RESULTS: Crude prevalence of probable/definite FH was 0.35% (0.29-0.41%), estimated by the Chinese modified DLCN definition. Prevalence in female was 0.38%, and in male, it was 0.32%. Age-standardized prevalence in female increased significantly around the age of 50 years. Moreover, there were no FH patients getting low-density lipoprotein cholesterol controlled to the recommended level. Multivariate logistic regression identified that older, overweight/obesity were positively associated with FH. CONCLUSIONS: The current study indicated that FH was not rare in rural area of China (1 in 286). Effective early detection and timely control of FH must be strengthened to reduce disease burden.


Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Programas de Rastreamento/métodos , População Rural/estatística & dados numéricos , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
7.
Lipids Health Dis ; 18(1): 80, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935416

RESUMO

BACKGROUND: Evidence regarding the correlation between lipoproteins and telomere length in US adults is limited. We aimed to investigate whether lipoproteins was associated with telomere length using US National Health and Nutrition Examination Survey (NHANES) database. METHODS: A total of 6468 selected participants were identified in the NHANES Data Base (1999-2002). The independent and dependent variables were lipoproteins and telomere length, respectively. The covariates included demographic data, dietary data, physical examination data, and comorbidities. RESULTS: In fully-adjusted model, we found that 0.1 differences of telomere length were positively associated with HDL-C [0.19 (95% CI 0.07, 0.31)], while the associations between LDL-C [0.19 (95% CI -0.27, 0.65)], TG [- 1.00 (95% CI -2.09, 0.07) and telomere length were not detected. By nonlinearity test, only the relationship between HDL-C and telomere length was nonlinear. The inflection point we got was 1.25. On the left side of the inflection point (telomere length ≤ 1.25), a difference in 0.1 of telomere length was associated with 0.50 difference in HDL-C. CONCLUSION: After adjusting for demographic data, dietary data, physical examination data, and comorbidities, telomere length is not associated with LDL-C and TG, but is positively associated with HDL-C when telomere length is less than 1.25.


Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Lipoproteínas/genética , Homeostase do Telômero/genética , Telômero/genética , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/patologia , Leucócitos/citologia , Leucócitos/metabolismo , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de Risco , Triglicerídeos/sangue
8.
Heart Vessels ; 34(10): 1595-1599, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30968218

RESUMO

Familial hypercholesterolemia (FH) is reportedly associated with the development of coronary artery disease (CAD), especially acute coronary syndrome (ACS). However, the prevalence of FH in patients with stable CAD is still unclear. The aim of this study was to investigate the prevalence of Achilles tendon xanthoma (ATX) and heterozygous FH in patients with stable CAD and ACS undergoing percutaneous coronary intervention (PCI). A total of 423 patients with CAD (273 stable CAD and 150 ACS) undergoing PCI at Chiba University Hospital between June 2016 and February 2018 were enrolled in this study. Soft X-ray radiography of the Achilles tendon was performed in all patients, and a maximum thickness of 9 mm or more is regarded as ATX. Heterozygous FH was diagnosed according to the Japan Atherosclerosis Society Guidelines. In comparisons between stable CAD and ACS patients, ATX was observed in 9.2% vs. 15.3% (p = 0.055), and heterozygous FH was diagnosed in 3.7% vs. 5.3% (p = 0.416), respectively. Among ACS patients, those with ST elevation myocardial infarction (STEMI) showed the highest prevalence of ATX (19.5%) and FH (7.3%). Whereas ATX and heterozygous FH were considerably observed in patients with ACS, a certain number of ATX and heterozygous FH were also detected in stable CAD patients.


Assuntos
Tendão do Calcâneo/diagnóstico por imagem , Doença da Artéria Coronariana/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Intervenção Coronária Percutânea , Xantomatose/epidemiologia , Idoso , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Raios X , Xantomatose/diagnóstico por imagem
9.
Atheroscler Suppl ; 36: 1-5, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30876526

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) is frequently underdiagnosed. Prevalence of the FH in Kyrgyzstan is unknown. AIM: to investigate the prevalence of FH amongst patients in the outpatient settings of the tertiary cardiologic center in Kyrgyzstan. METHODS: Retrospective observational study was conducted using the database of the laboratory of biochemistry and electronic database of outpatient department of the National Center of Cardiology and internal diseases. Patient with the level of total cholesterol (TC) ≥7,5 mmol/l and/or low density lipoprotein cholesterol (LDL-C) ≥ 4,9 mmol/l without signs of secondary hyperlipidemia were included in the analysis. FH was defined using Dutch Lipid Clinic Network criteria. RESULTS: according to the laboratory database levels of TC and LDL-C was conducted in 8281patiens and 525 of them had a high lipid levels. After exclusion of patients with secondary hyperlipidemia, high level of triglycerides and pregnant women - 91 patients were included in the analysis. Among them the definite FH was revealed in 2 (2,2%) patients, probable FH - in 6 (6,6%), and possible in 76 (83,5%), and in 7,7% there were no signs of FH. CONCLUSION: Frequency of potential FH (definite and probable) in our analysis was low. To understand the real prevalence of FH in a Kyrgyz population epidemiological study is needed.


Assuntos
Instituições de Assistência Ambulatorial , Hiperlipoproteinemia Tipo II/epidemiologia , Centros de Atenção Terciária , Idoso , Biomarcadores/sangue , LDL-Colesterol/sangue , Bases de Dados Factuais , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Quirguistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Estudos Retrospectivos
10.
Atheroscler Suppl ; 36: 24-27, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30876529

RESUMO

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant condition raising the risk of premature cardiovascular disease up to twentyfold.[1] [2] It is under-diagnosed and undertreated, in spite of availability of effective treatment. Registers are recommended to assist in the recognition and improvement of the condition since treatment reduces morbidity and mortality. Disease registers enable longitudinal review and the application of continuous quality improvement methodology. The aims of this paper are to describe the process of setting up a new FH register in Malta based on phenotype, the preliminary results achieved, the barriers encountered, how these were overcome, and future plans for development. METHODS: The registry was established as an observational clinical study designed for a small healthcare system with limited resources. Effective process design requires attention to standards, capacity, outcome measurement and feedback, which have been incorporated. RESULTS: 43 individuals have been registered applying Dutch Lipid Clinic Network standards, including 9 Definite, 16 Probable and 18 Possible FH. Cascade testing has identified three younger, and one older FH individuals; amenable risk factors and target outcomes are available for feedback and action. Barriers included insufficient infrastructure, limited stakeholder involvement, time limitations impacting clinical care and data collection, poor recognition, awareness and referral, and limited cascade testing. Overcoming these required persistence, reorganizing clinical work, with some assistance from clinic nurses, forward planning to involve patients and raising FH awareness through presentations to various audiences. CONCLUSIONS: During this year the register was established and is functional: awareness is being raised. Future steps will target process improvement for effectiveness and sustainability.


Assuntos
LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II , Sistema de Registros , Projetos de Pesquisa , Adulto , Idoso , Anticolesterolemiantes/uso terapêutico , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Masculino , Malta/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Dados Preliminares , Prognóstico , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Adulto Jovem
11.
Atheroscler Suppl ; 36: 28-30, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30876530

RESUMO

Familial hypercholesterolemia is an Mendelian dominant disorder characterized by defects of the low density lipoprotein receptor (LDLR) that result in a defective removal of LDL from plasma, which promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and arteries (atherosclerosis). Diagnosis severe clinical phenotype FH with Dutch Lipid Clinic Network Criteria, encompassing history of premature ASCVD, tendon xanthomas, and a family history of hypercholesterolemia and premature ASCVD in relatives is rare in the Portuguese FH patients. There is a variability of the phenotype in FH individuals with clinical diagnosis or genetic mutation (carriers and patients) probably due to environmental factors in the last century, a Mediterranean diet, or a diet without fat food, trans fat food, no smoking, no sedentary life that can interfere with our metabolism, or are consequences of polygenic, epigenetic, acquired defects, modifiers genes and beta-globin asymptomatic carriers. We have several concepts/mechanisms in genetics that are transversal to hereditary diseases and common in FH, such as somatic mosaicism, germinal mosaicism, variable expression and variable penetrance of mutations. A negative blood genetic test result does not exclude FH, because the pathogenic LDLR mutation can be expressed only in the liver (a mutation in somatic tissue) or occasionally there is a vertical transmission from partner to future child by a mutation on germinal line - germinal mosaicism. Unlike north European countries, the most FH carriers and patients had less severe phenotypes, for example with have children and young adult carriers with LDL-R mutation had normal TC and LDL-C, old women had a milder phenotype without ASCVD events, tendon xanthomas are seen in <1% patients, and most homozygous FH patients are under combined therapy.


Assuntos
LDL-Colesterol/sangue , Interação Gene-Ambiente , Hiperlipoproteinemia Tipo II/genética , Penetrância , Receptores de LDL/genética , Adulto , Idoso de 80 Anos ou mais , Dieta com Restrição de Gorduras , Dieta Mediterrânea , Exercício , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Hereditariedade , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Portugal/epidemiologia , Fatores de Risco , Resultado do Tratamento
12.
Atheroscler Suppl ; 36: 31-36, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30876531

RESUMO

BACKGROUND AND AIMS: Inherited familial hypercholesterolemia (FH) increases cardiovascular risks, but perceived depression in FH is unknown. This study aims to explore the association between the FH and perceived depression. METHODS: This study was a hospital-based design, we started to recruit clinical diagnosis of phenotypic FH since 2014 for the Ten Countries Study in the Asia-Pacific region. We consecutively recruited 302 FH patients and other 414 comparison subjects (214 subjects with hypertriglyceridemia and 200 subjects with normal lipid controls) from the special lipid clinic of National Taiwan University Hospital, Taipei. All participants received cardiovascular health examinations and completed a self-reported questionnaire, including the Center for Epidemiologic Studies Depression Scale (CES-D) for assessment of the psychosocial depression. RESULTS: Clinical FH patients had a higher risk of perceived depression, with an odds ratio (95% confidence intervals) of possible depression by 1.50 (1.07-2.11) and probable depression by 1.73 (1.10-2.75) than those of the non-FH groups after adjusted relevant cardiovascular risk factors. FH patients with a family history of coronary heart disease (CHD) had higher domain-specific depression scores than those of controls. In addition, this study found that FH patients with lower educational levels also had a higher risk of depression compared with those in control groups. CONCLUSIONS: Patients with clinical phenotype of FH are associated with subjectively perceived depression, particularly among FH patients with a family history of CHD.


Assuntos
Afeto , LDL-Colesterol/sangue , Depressão/psicologia , Hiperlipoproteinemia Tipo II/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Prognóstico , Medição de Risco , Fatores de Risco , Taiwan/epidemiologia
13.
JAMA Netw Open ; 2(3): e190318, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30848806

RESUMO

Importance: Which cardiometabolic risk factors (eg, hypertension, type 2 diabetes, overweight or obesity, and dyslipidemia) are more sensitive to long-term exposure to ambient air pollution and whether participants with these conditions are more susceptible to the cardiovascular effects of air pollution remain unclear. Objectives: To evaluate the associations among long-term exposure to air pollutants, cardiometabolic risk factors, and cardiovascular disease (CVD) prevalence. Design, Setting, and Participants: This population-based cross-sectional study was conducted from April 1 through December 31, 2009, in 3 cities in Northeastern China. Participants were adults aged 18 to 74 years who had lived in study area for 5 years or longer. Data analysis was performed from May 1 through December 31, 2018. Exposures: Long-term (2006-2008) exposure to air pollutants was measured using a spatiotemporal statistical model (particulate matter with an aerodynamic diameter of ≤2.5 µm [PM2.5] and ≤1.0 µm [PM1.0]) and data from air monitoring stations (particulate matter with an aerodynamic diameter of ≤10.0 µm [PM10.0], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]). Main Outcomes and Measures: Cardiovascular disease was determined by self-report of physician-diagnosed CVD. Blood pressure, body mass index, and levels of triglycerides and low-density lipoprotein cholesterol were measured using standard methods. Results: Participants included 15 477 adults (47.3% women) with a mean (SD) age of 45.0 (13.5) years. The prevalence of CVD was 4.8%, and the prevalence of cardiometabolic risk factors ranged from 8.6% (hyperbetalipoproteinemia) to 40.5% (overweight or obesity). Mean (SD) air pollutant concentrations ranged from 35.3 (5.5) µg/m3 (for NO2) to 123.1 (14.6) µg/m3 (for PM10.0). Associations with air pollutants were identified for individuals with hyperbetalipoproteinemia (eg, odds ratio [OR], 1.36 [95% CI, 1.03-1.78] for a 10-µg/m3 increase in PM1.0) and the weakest association for those with for overweight or obesity (eg, OR, 1.06 [95% CI, 1.02-1.09] for a 10-µg/m3 increase in PM1.0). Cardiometabolic risk factors only partially mediated associations between air pollution and CVD. However, they modified the associations such that greater associations were found in participants with these cardiometabolic conditions (eg, ORs for CVD and per 10-µg/m3 increase in PM1.0, 1.22 [95% CI, 1.12-1.33] in participants with hyperbetalipoproteinemia and 1.07 [95% CI, 0.98-1.16] in participants without hyperbetalipoproteinemia). Conclusions and Relevance: In this population-based study of Chinese adults with CVD, long-term exposure to air pollution was associated with a higher prevalence of cardiometabolic risk factors, and the strongest associations were observed for hyperbetalipoproteinemia. In addition, participants with cardiometabolic risk factors may have been more vulnerable to the effects of air pollution on CVD.


Assuntos
Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Exposição por Inalação , Material Particulado , Adulto , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Doenças Cardiovasculares/classificação , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , China/epidemiologia , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Exposição por Inalação/prevenção & controle , Masculino , Pessoa de Meia-Idade , Material Particulado/efeitos adversos , Material Particulado/análise , Prevalência , Fatores de Risco , Tempo
14.
J Am Coll Cardiol ; 73(9): 1029-1039, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30846097

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Cascade testing is recommended for FH, but there are no similar recommendations for elevated Lp(a). OBJECTIVES: This study investigated whether testing for Lp(a) was effective in detecting and risk stratifying individuals participating in an FH cascade screening program. METHODS: Family members (N = 2,927) from 755 index cases enrolled in SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) were tested for genetic FH and elevated Lp(a) via an established screening program. Elevated Lp(a) was defined as levels ≥50 mg/dl. The authors compared the prevalence and yield of new cases of high Lp(a) in relatives of FH probands both with and without high Lp(a), and prospectively investigated the association between elevated Lp(a) and ASCVD events among family members. RESULTS: Systematic screening from index cases with both FH and elevated Lp(a) identified 1 new case of elevated Lp(a) for every 2.4 screened. Opportunistic screening from index cases with FH, but without elevated Lp(a), identified 1 individual for 5.8 screened. Over 5 years' follow-up, FH (hazard ratio [HR]: 2.47; p = 0.036) and elevated Lp(a) (HR: 3.17; p = 0.024) alone were associated with a significantly increased risk of experiencing an ASCVD event or death compared with individuals with neither disorder; the greatest risk was observed in relatives with both FH and elevated Lp(a) (HR: 4.40; p < 0.001), independent of conventional risk factors. CONCLUSIONS: Testing for elevated Lp(a) during cascade screening for FH is effective in identifying relatives with high Lp(a) and heightened risk of ASCVD, particularly when the proband has both FH and elevated Lp(a).


Assuntos
Testes Genéticos/métodos , Hiperlipoproteinemia Tipo II/sangue , Lipoproteína(a)/sangue , Adulto , Biomarcadores/sangue , DNA/genética , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Prevalência , Estudos Prospectivos , Receptores de LDL/genética , Receptores de LDL/metabolismo , Fatores de Risco , Espanha/epidemiologia
16.
J Pediatr Nurs ; 44: 50-55, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30683281

RESUMO

PROBLEM: Cardiovascular disease (CVD) is the leading cause of death in the U.S. and in most Western countries. Early identification and treatment of individuals with elevated levels of atherogenic cholesterol, a major contributor to CVD, have been shown to be effective and safe in reducing premature morbidity and mortality, especially in familial hypercholesterolemia (FH). Cholesterol screening of youth also provides a unique means of identifying affected family members through reverse cascade screening (RCS). ELIGIBILITY CRITERIA: A PubMed review of all relevant articles from 2000 to 2016 was conducted of familial hypercholesterolemia and cholesterol screening of youth. RESULTS: We provide an overview of cholesterol screening, outline the role of the pediatric nurse in the lipid clinic, and discuss effectiveness and potential barriers, including cost and confidentiality considerations of RCS. CONCLUSIONS: Early identification and effective intervention of youth with FH, including adoption of a heart-healthy lifestyle, has the potential of 1) markedly reducing or eliminating atherosclerotic cardiovascular disease and related events in future generations and 2) provides a unique means of identifying affected family members. IMPLICATIONS: Pediatric nurses play a vital role in the education and care coordination of children diagnosed with FH and screening of relatives. Identification of a child with FH with effective screening of relatives combines the benefits of universal and cascade screening, and has the potential of detecting all living cases of FH. While potentially providing significant benefit to those at risk for premature CVD, a RCS program needs to carefully consider ethical, psychological, and financial implications as well.


Assuntos
Diagnóstico Precoce , Predisposição Genética para Doença/epidemiologia , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Programas de Rastreamento/métodos , Adolescente , Fatores Etários , Doenças Cardiovasculares/prevenção & controle , Criança , Feminino , Seguimentos , Testes Genéticos/métodos , Humanos , Hiperlipoproteinemia Tipo II/genética , Incidência , Masculino , Programas de Rastreamento/enfermagem , Papel do Profissional de Enfermagem , Enfermagem Pediátrica/métodos , Medição de Risco , Fatores Sexuais
17.
Nurse Pract ; 44(2): 18-24, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30614895

RESUMO

If undiagnosed and untreated, familial hypercholesterolemia can lead to serious cardiac complications, such as premature atherosclerotic cardiovascular disease. NPs should be familiar with the clinical presentation of this inherited metabolic disease to diagnose patients as early as possible and promptly begin treatment that may include lifestyle changes, statin therapy, and/or nonstatin therapy.


Assuntos
Hiperlipoproteinemia Tipo II/enfermagem , Diagnóstico Precoce , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/fisiopatologia , Profissionais de Enfermagem , Diagnóstico de Enfermagem
18.
Clin Cardiol ; 42(3): 385-390, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30637778

RESUMO

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic cause of premature myocardial infarction (PMI). Early diagnosis of FH is critical for prognosis. HYPOTHESIS: To investigate the prevalence of FH among a cohort of Chinese patients with PMI using genetic testing, and to evaluate different diagnostic criteria. METHODS: A total of 225 consecutive PMI patients were recruited. Low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin-kexin type 9 (PCSK9) and low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) genes were detected by Sanger sequencing. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria and modified DLCN criteria, respectively. The prevalence and clinical features of FH were analyzed. RESULTS: In all PMI patients, pathogenic mutations of LDLR, APOB, PCSK9 and LDLRAP1 genes were found in 10 of 225 patients. Among all mutations, four mutations (LDLR c.129G>C, LDLR c.1867A>T, LDLRAP1 c.65G>C, and LDLRAP1 c.274G>A) were newly discovered. The prevalence of FH diagnosed by genetic testing was 4.4%. The prevalence of definite/probable FH diagnosed by DLCN and modified DLCN criteria reached 8.0% and 23.6%, respectively, and the mutation rates were 33.3% and 12.2%, respectively. The low-density lipo-protein cholesterol (LDL-C) levels in PMI patients with FH were far from goal attainment. Only one of the FH patients had LDL-C <2.5 mmol/L, and none of them had LDL-C <1.8 mmol/L. CONCLUSIONS: The prevalence of FH among Chinese patients with PMI appeared relatively common. Underdiagnosis and undertreatment of FH are still a big problem, which should arouse a widespread concern.


Assuntos
Diagnóstico Precoce , Testes Genéticos/métodos , Hiperlipoproteinemia Tipo II/epidemiologia , Infarto do Miocárdio/etiologia , Biomarcadores/sangue , China/epidemiologia , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Lipoproteínas/sangue , Lipoproteínas/genética , Masculino , Pessoa de Meia-Idade , Mutação , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Fenótipo , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco
19.
Nat Rev Cardiol ; 16(1): 9-20, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29973710

RESUMO

Familial hypercholesterolaemia is the most commonly encountered genetic condition that predisposes individuals to premature cardiovascular disease. Nevertheless, most patients are undiagnosed, and treatment is often suboptimal even when the diagnosis seems certain. Advances in molecular technologies are reshaping our understanding of this condition, including revision upwards of the population prevalence. Furthermore, the underlying pathophysiological complexity has been exposed by the range of causative genetic loci, breadth of types and classes of rare disease-causing variants, and polygenic basis of the phenotype in many patients. Genetic testing is not always helpful or definitive. Familial hypercholesterolaemia can be envisioned as a group of related disorders, of which the classic 'textbook' phenotype is a subset. Features such as clinical stigmata, family history of dyslipidaemia or cardiovascular disease, and presence of a rare pathogenic variant all increase diagnostic certainty. However, even in the absence of these elements, the essential feature remains an elevated level of plasma LDL cholesterol, which alone should prompt a dialogue between the care provider and the patient on lifestyle modification and lipid-lowering therapy as the foundation of a long-term strategy to prevent or delay the onset of cardiovascular disease.


Assuntos
LDL-Colesterol/sangue , Marcadores Genéticos , Hiperlipoproteinemia Tipo II/genética , Animais , Biomarcadores/sangue , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/terapia , Fenótipo , Prognóstico , Fatores de Risco
20.
Genet Med ; 21(5): 1173-1180, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30270359

RESUMO

PURPOSE: Large-scale, population-based biobanks integrating health records and genomic profiles may provide a platform to identify individuals with disease-predisposing genetic variants. Here, we recall probands carrying familial hypercholesterolemia (FH)-associated variants, perform cascade screening of family members, and describe health outcomes affected by such a strategy. METHODS: The Estonian Biobank of Estonian Genome Center, University of Tartu, comprises 52,274 individuals. Among 4776 participants with exome or genome sequences, we identified 27 individuals who carried FH-associated variants in the LDLR, APOB, or PCSK9 genes. Cascade screening of 64 family members identified an additional 20 carriers of FH-associated variants. RESULTS: Via genetic counseling and clinical management of carriers, we were able to reclassify 51% of the study participants from having previously established nonspecific hypercholesterolemia to having FH and identify 32% who were completely unaware of harboring a high-risk disease-associated genetic variant. Imaging-based risk stratification targeted 86% of the variant carriers for statin treatment recommendations. CONCLUSION: Genotype-guided recall of probands and subsequent cascade screening for familial hypercholesterolemia is feasible within a population-based biobank and may facilitate more appropriate clinical management.


Assuntos
Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Programas de Rastreamento/métodos , Apolipoproteína B-100/genética , Bancos de Espécimes Biológicos , Estônia/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Mutação , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Análise de Sequência de DNA
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