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2.
Eur Heart J ; 39(5): 385-393, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29228164

RESUMEN

Aims: In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results: In a cohort study of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2.41 (1.28-4.51)(P-trend = 0.004). The corresponding OR for IHD in individuals with vs. without NAFLD was 1.65 (1.34-2.04)(P = 3×10-6). PNPLA3 I148M was associated with a stepwise increase in liver fat content of up to 28% in MM vs. II-homozygotes (P-trend = 0.0001) and with ORs of 2.03 (1.52-2.70) for NAFLD (P = 3×10-7), 3.28 (2.37-4.54) for cirrhosis (P = 4×10-12), and 0.95 (0.86-1.04) for IHD (P = 0.46). In agreement, in meta-analysis (N = 279 013/IHD = 71 698), the OR for IHD was 0.98 (0.96-1.00) per M-allele vs. I-allele. The OR for IHD per M-allele higher genetically determined liver fat content was 0.98 (0.94-1.03) vs. an observational estimate of 1.05 (1.02-1.09)(P for comparison = 0.02). Conclusion: Despite confirming the known observational association of liver fat content and NAFLD with IHD, lifelong, genetically high liver fat content was not causally associated with risk of IHD. These results suggest that the observational association is due to confounding or reverse causation.


Asunto(s)
Isquemia Miocárdica , Enfermedad del Hígado Graso no Alcohólico , Anciano , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Humanos , Hígado/patología , Masculino , Análisis de la Aleatorización Mendeliana , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Factores de Riesgo
3.
BMC Infect Dis ; 16(1): 713, 2016 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-27887644

RESUMEN

BACKGROUND: Modern combination antiretroviral therapy (cART) has improved survival for people living with HIV (PLWHIV). Non-AIDS comorbidities have replaced opportunistic infections as leading causes of mortality and morbidity, and are becoming a key health concern as this population continues to age. The aim of this study is to estimate the prevalence and incidence of non-AIDS comorbidity among PLWHIV in Denmark in the cART era and to determine risk factors contributing to the pathogenesis. The study primarily targets cardiovascular, respiratory, and hepatic non-AIDS comorbidity. METHODS/DESIGN: The Copenhagen comorbidity in HIV-infection (COCOMO) study is an observational, longitudinal cohort study. The study was initiated in 2015 and recruitment is ongoing with the aim of including 1500 PLWHIV from the Copenhagen area. Follow-up examinations after 2 and 10 years are planned. Uninfected controls are derived from the Copenhagen General Population Study (CGPS), a cohort study including 100,000 uninfected participants from the same geographical region. Physiological and biological measures including blood pressure, ankle-brachial index, electrocardiogram, spirometry, exhaled nitric oxide, transient elastography of the liver, computed tomography (CT) angiography of the heart, unenhanced CT of the chest and upper abdomen, and a number of routine biochemical analysis are uniformly collected in participants from the COCOMO study and the CGPS. Plasma, serum, buffy coat, peripheral blood mononuclear cells (PBMC), urine, and stool samples are collected in a biobank for future studies. Data will be updated through periodical linking to national databases. DISCUSSION: As life expectancy for PLWHIV improves, it is essential to study long-term impact of HIV and cART. We anticipate that findings from this cohort study will increase knowledge on non-AIDS comorbidity in PLWHIV and identify targets for future interventional trials. Recognizing the demographic, clinical and pathophysiological characteristics of comorbidity in PLWHIV may help inform development of new guidelines and enable us to move forward to a more personalized HIV care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02382822 .


Asunto(s)
Infecciones por VIH/epidemiología , Estudios Observacionales como Asunto , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Adulto , Presión Sanguínea , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Comorbilidad , Angiografía por Tomografía Computarizada , Dinamarca/epidemiología , Infecciones por VIH/tratamiento farmacológico , Humanos , Leucocitos Mononucleares , Esperanza de Vida , Hepatopatías/epidemiología , Estudios Longitudinales , Factores de Riesgo
4.
Ugeskr Laeger ; 171(15): 1275-81, 2009 Apr 06.
Artículo en Danés | MEDLINE | ID: mdl-19416618

RESUMEN

Noninvasive evaluation of the coronary arteries by multi-detector row computed tomography is a promising new alternative to conventional invasive coronary angiography. This article describes the technical background, methods, limitations and clinical applications and reviews current literature that compares the diagnostic accuracy of multi-detector row computed tomography with that of coronary angiography.


Asunto(s)
Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Contraindicaciones , Humanos , Imagenología Tridimensional , Valor Predictivo de las Pruebas , Dosis de Radiación , Sensibilidad y Especificidad
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