Acilcarnitinas en plasma y riesgo de insuficiencia cardiaca y fibrilación auricular: el estudio Prevención con dieta mediterránea / Plasma acylcarnitines and risk of incident heart failure and atrial fibrillation: the Prevención con dieta mediterránea study

Introducción y objetivos La desregulación del metabolismo de los ácidos grasos en la mitocondria es un mecanismo involucrado en el desarrollo de insuficiencia cardiaca (IC) y fibrilación auricular (FA). Se evaluó la asociación entre la concentración plasmática de acilcarnitinas y la incidencia de IC o FA y si la dieta mediterránea (DietMed) puede atenuar la asociación entre las acilcarnitinas y el riesgo de IC o FA. Métodos Dos estudios de casos y controles anidados en el ensayo Prevención con dieta mediterránea (PREDIMED). Se incluyó a participantes con elevado riesgo cardiovascular en España: 326 casos incidentes de IC y 509 de FA se emparejaron individualmente con 1 a 3 controles. Las acilcarnitinas en plasma se midieron con espectrometría de masas en tándem con cromatografía líquida de alta resolución. Se ajustaron modelos de regresión logística condicional para estimar las OR multivariables y los IC95%. Se evaluaron interacciones multiplicativas y aditivas por el grupo de intervención, obesidad (índice de masa corporal ≥ 30) y diabetes mellitus tipo 2. Resultados Las altas concentraciones de acilcarnitinas de cadena mediana y larga se asociaron con un mayor riesgo de IC (respectivamente, ORporDE ajustada=1,28; IC95%, 1,09-1,51, y ORporDE ajustada=1,21; IC95%, 1,04-1,42). Se observó una asociación significativa entre las acilcarnitinas de cadena larga y el riesgo de FA: 1,20 (1,06-1,36). Se encontró una interacción aditiva entre las acilcarnitinas de cadena larga y la FA con la DietMed suplementada con aceite de oliva virgen extra (p de interacción=0,036) y con la obesidad (p=0,022) de forma inversa y directa respectivamente. Conclusiones En las personas con alto riesgo cardiovascular, las altas concentraciones de acilcarnitinas de cadena larga se asocian con mayor riesgo de IC y FA incidentes. Una intervención con DietMed+aceite de oliva virgen extra puede reducir el riesgo asociado con las acilcarnitinas de cadena larga (AU)

Introduction and objectives Fatty acid metabolic dysregulation in mitochondria is a common mechanism involved in the development of heart failure (HF) and atrial fibrillation (AF). We evaluated the association between plasma acylcarnitine levels and the incidence of HF or AF, and whether the mediterranean diet (MedDiet) may attenuate the association between acylcarnitines and HF or AF risk. Methods Two case-control studies nested within the Prevención con dieta mediterránea (PREDIMED) trial. High cardiovascular risk participants were recruited in Spain: 326 incident HF and 509 AF cases individually matched to 1 to 3 controls. Plasma acylcarnitines were measured with high-throughput liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were fitted to estimate multivariable OR and 95%CI. Additive and multiplicative interactions were assessed by intervention group, obesity (body mass index ≥ 30 kg/m2), and type 2 diabetes. Results Elevated levels of medium- and long-chain acylcarnitines were associated with increased HF risk (adjusted ORperDE, 1.28; 95%CI, 1.09-1.51 and adjusted ORperDE, 1.21; 95%CI, 1.04-1.42, respectively). A significant association was observed for AF risk with long-chain acylcarnitines: 1.20 (1.06-1.36). Additive interaction of the association between long-chain acylcarnitines and AF by the MediDiet supplemented with extra virgin olive oil (P for additive interaction=.036) and by obesity (P=.022) was observed in an inverse and direct manner, respectively. Conclusions Among individuals at high cardiovascular risk, elevated long-chain acylcarnitines were associated with a higher risk of incident HF and AF. An intervention with MedDiet+extra-virgin olive oil may reduce AF risk associated with long-chain acylcarnitines (AU)

Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology.

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

Association between omentin-1, adiponectin and bone health under consideration of osteoprotegerin as possible mediator.

PURPOSE: Several studies implicated a crosstalk between bone and fat in the pathogenesis of osteoporosis. Few studies indicated an association between adiponectin and omentin-1 on the bone remodeling process and bone mineral density, and suggested osteoprotegerin (OPG) as a mediator of this relationship. However, only limited evidence on this relationship is available in humans. Therefore, this study aimed to investigate the association between omentin-1, adiponectin and broadband ultrasound attenuation (BUA) in peri-/premenopausal and postmenopausal women, and to assess the role of OPG as a possible mediator. METHODS: Data from the German population-based EPIC-Potsdam cohort comprising 637 women were analyzed. Multivariable-adjusted ANCOVA including age, BMI, waist circumference, smoking status, education, physical activity, adiponectin or omentin-1 and hormone use was used to investigate potential relationships between the adipokines and BUA levels. A mediation analysis assessed the mediating effect of OPG on the association of BUA and omentin-1 levels. RESULTS: Peri-/premenopausal women had higher BUA levels (112.5 ± 10.1 dB/MHz), compared to postmenopausal women (106.3 ± 10.0 dB/MHz). In peri-/premenopausal women neither adiponectin nor omentin-1 was significantly associated with BUA. In postmenopausal women, adiponectin was not associated with BUA, but 10 % increase in the omentin-1 concentration was significantly associated with 0.44 dB/MHz lower BUA levels (p = 0.01). Omentin-1 was positively associated with OPG (p = 0.02); however, OPG was not significantly related to BUA (p = 0.62). CONCLUSION: Our study provides evidence for an inverse association between circulating omentin-1 and BUA levels in postmenopausal women. However, the present findings do not support a mediating effect of OPG in the adipose tissue-bone pathway.