| 1. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 2. |
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| 3. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 4. |
- 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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| 5. |
- Mandelzweig, Lori, et al.
(författare)
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The second Euro Heart Survey on acute coronary syndromes : Characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004
- 2006
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:19, s. 2285-2293
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Our study aimed to examine the management of acute coronary syndromes (ACS) in Europe and the Mediterranean basin, and to compare adherence to guidelines with that reported in the first Euro Heart Survey on ACS (EHS-ACS-I), 4 years earlier. METHODS AND RESULTS: In a prospective survey conducted in 2004 (EHS-ACS-II), data describing the characteristics, treatment, and outcome of 6385 patients diagnosed with ACS in 190 medical centres in 32 countries were collected. ACS with ST-elevation was the initial diagnosis in 47% of patients, no ST-elevation in 48%, and undetermined electrocardiographic pattern in 5% of patients. Comparison of data collected in 2000 and 2004 showed similar baseline characteristics, but greater use of recommended medications and coronary interventions in EHS-ACS-II. Among patients with ST-elevation, the use of primary reperfusion increased slightly (from 56 to 64%), with a significant shift from fibrinolytic therapy to primary percutaneous coronary intervention (PPCI). The use of PPCI rose from 37 to 59% among those undergoing primary reperfusion therapy. Analysis of data in 34 centres that participated in both surveys showed even greater improvement with respect to the use of recommended medical therapy, interventions, and outcome. CONCLUSION: Data from EHS-ACS-II suggest an increase in adherence to guidelines for treatment of ACS in comparison with EHS-ACS-I.
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| 6. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 7. |
- Pocock, Stuart, et al.
(författare)
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International differences in treatment effect : do they really exist and why?
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:24, s. 1846-1852
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Tidskriftsartikel (refereegranskat)abstract
- With the increasing globalization of clinical trials, the opportunity exists to explore potential geographic differences in treatment effect within any major trial. Such geographic differences may arise because of international differences in patient selection, medical practice, or evaluation of outcomes, and such international variations need better documentation in trial reports. Appropriate pre-defined statistical analyses, including statistical tests of interaction regarding geographic heterogeneity in treatment effect, are important. Geographic variations are a particularly tricky form of subgroup analysis: they lack statistical power, are at best hypothesis-generating and can generate more confusion than insight. Referring to key examples, e.g. the PLATO and MERIT-HF, we emphasize the need for caution in interpreting evidence of potential geographic inconsistencies in treatment effect. Although it is appropriate to explore any biological or practical reasons for apparent geographic anomalies in treatment effect, the play of chance is often the most plausible and wise interpretation.
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| 8. |
- 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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| 9. |
- Viadas, Raul, et al.
(författare)
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Association of physical activity with high-density lipoprotein functionality in a population-based cohort : the REGICOR study
- 2023
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Ingår i: Revista Española de Cardiología. - : Elsevier BV. - 0300-8932 .- 1579-2242. ; 76:2, s. 86-93
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Tidskriftsartikel (refereegranskat)abstract
- Introduction and objectives: To determine the dose-response association between current and past leisure-time physical activity (LTPA), total and at different intensities, and high-density lipoprotein (HDL) functionality parameters.Methods: Study participants (n = 642) were randomly drawn from a large population-based survey. Mean age of the participants was 63.2 years and 51.1% were women. The analysis included data from a baseline and a follow-up visit (median follow-up, 4 years). LTPA was assessed using validated questionnaires at both visits. Two main HDL functions were assessed: cholesterol efflux capacity and HDL antioxidant capacity, at the follow-up visit. Linear regression and linear additive models were used to assess the linear and nonlinear association between LTPA and HDL functionality.Results: Total LTPA at follow-up showed an inverse and linear relationship between 0 and 400 METs x min/d with HDL antioxidant capacity (regression coefficient [beta]:-0.022; 95%CI,-0.030,-0.013), with a plateau above this threshold. The results were similar for moderate (beta:-0.028; 95%CI,-0.049, -0.007) and vigorous (beta:-0.025; 95%CI,-0.043,-0.007), but not for light-intensity LTPA. LTPA at follow-up was not associated with cholesterol efflux capacity. Baseline LTPA was not associated with any of the HDL functionality parameters analyzed.Conclusions: Current moderate and vigorous LTPA showed a nonlinear association with higher HDL antioxidant capacity. Maximal benefit was observed with low-intermediate doses of total LTPA (up to 400 METs x min/d). Our results agree with current recommendations for moderate-vigorous LTPA practice and suggest an association between PA and HDL functionality in the general population.
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| 10. |
- Voight, Benjamin F, et al.
(författare)
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Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
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