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- Fernandez-Sanles, Alba, et al.
(författare)
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DNA methylation biomarkers of myocardial infarction and cardiovascular disease
- 2021
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Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083 .- 1868-7075. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The epigenetic landscape underlying cardiovascular disease (CVD) is not completely understood and the clinical value of the identified biomarkers is still limited. We aimed to identify differentially methylated loci associated with acute myocardial infarction (AMI) and assess their validity as predictive and causal biomarkers.Results: We designed a case-control, two-stage, epigenome-wide association study on AMI (n(discovery) = 391, n(validation) = 204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. We performed a fixed-effects meta-analysis of the two samples. 34 CpGs were associated with AMI. Only 12 of them were available in two independent cohort studies (n similar to 1800 and n similar to 2500) with incident coronary and cardiovascular disease (CHD and CVD, respectively). The Infinium HumanMethylation450 BeadChip was used in those two studies. Four of the 12 CpGs were validated in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. We then assessed whether methylation risk scores based on those CpGs improved the predictive capacity of the Framingham risk function, but they did not. Finally, we aimed to study the causality of those associations using a Mendelian randomization approach but only one of the CpGs had a genetic influence and therefore the results were not conclusive.Conclusions: We have identified 34 CpGs related to AMI. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to AMI. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.
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| 2. |
- Prats-Uribe, Albert, et al.
(författare)
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High-density lipoprotein characteristics and coronary artery disease : a Mendelian randomization study
- 2020
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Ingår i: Metabolism. - : W B SAUNDERS CO-ELSEVIER INC. - 0026-0495 .- 1532-8600. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- Background: To assess whether genetically determined quantitative and qualitative HDL characteristics were independently associated with coronary artery disease (CAD). Methods: We designed a two-sample multivariate Mendelian randomization study with available genome-wide association summary data. We identified genetic variants associated with HDL cholesterol and apolipoprotein A-I levels, HDL size, particle levels, and lipid content to define our genetic instrumental variables in one sample (Kettunen et al. study, n = 24,925) and analyzed their association with CAD risk in a different study (CARDloGRAMplusC4D, n = 184,305). We validated these results by defining our genetic variables in another database (METSINI, n = 8372) and studied their relationship with CAD in the CARDloGRAMplusC4D dataset. To estimate the effect size of the associations of interest adjusted for other lipoprotein traits and minimize potential pleiotropy, we used the Multi-trait-based Conditional & Joint analysis. Results: Genetically determined HDL cholesterol and apolipoprotein A-I levels were not associated with CAD. HDL mean diameter (beta = 027 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (beta = 0.29 (95%CI = 0.17; 0.40]), and triglyceride content in very large HDIs (beta = 0.14 [95%CI = 0.040; 025]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (beta = -0.076 [95%CI = -0.10; -0.052]) was inversely related to this risk. These results were validated in the METSIM-CARDloGRAMplu5C4D data. Conclusions: Some qualitative HDL characteristics (related to size, particle distribution, and cholesterol and triglyceride content) are related to CAD risk while HDL cholesterol levels are not. (C) 2020 Elsevier Inc. All rights reserved.
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| 3. |
- Sanllorente, Albert, et al.
(författare)
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A lifestyle intervention with an energy-restricted Mediterranean diet and physical activity enhances HDL function : a substudy of the PREDIMED-Plus randomized controlled trial
- 2021
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Ingår i: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 114:5, s. 1666-1674
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Consumption of a Mediterranean diet, adequate levels of physical activity, and energy-restricted lifestyle interventions have been individually associated with improvements in HDL functions. Evidence of intensive interventions with calorie restriction and physical activity is, however, scarce. OBJECTIVES: To determine whether an intensive lifestyle intervention with an energy-restricted Mediterranean diet plus physical activity enhanced HDL function compared to a non-hypocaloric Mediterranean eating pattern without physical activity. METHODS: In 391 older adults with metabolic syndrome (mean age, 65 years; mean BMI, 33.3 kg/m2) from 1 of the Prevención con Dieta Mediterránea-Plus trial centers, we evaluated the impact of a 6-month intervention with an energy-restricted Mediterranean diet plus physical activity (intensive lifestyle; n = 190) relative to a nonrestrictive Mediterranean diet without physical activity (control; n = 201) on a set of HDL functional traits. These included cholesterol efflux capacity, HDL oxidative/inflammatory index, HDL oxidation, and levels of complement component 3, serum amyloid A, sphingosine-1-phosphate, triglycerides, and apolipoproteins A-I, A-IV, C-III, and E in apoB-depleted plasma. RESULTS: The intensive-lifestyle intervention participants displayed greater 6-month weight reductions (-3.83 kg; 95% CI: -4.57 to -3.09 kg) but no changes in HDL cholesterol compared with control-diet participants. Regarding HDL functional traits, the intensive lifestyle decreased triglyceride levels (-0.15 mg/g protein; 95% CI: -0.29 to -0.014 mg/g protein) and apoC-III (-0.11 mg/g protein; 95% CI: -0.18 to -0.026 mg/g protein) compared to the control diet, with weight loss being the essential mediator (proportions of mediation were 77.4% and 72.1% for triglycerides and apoC-III levels in HDL, respectively). CONCLUSIONS: In older adults with metabolic syndrome, an energy-restricted Mediterranean diet plus physical activity improved the HDL triglyceride metabolism compared with a nonrestrictive Mediterranean diet without physical activity. This trial is registered at isrctn.com as ISRCTN89898870.
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