| 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. |
- 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. - : eLife Sciences Publications Ltd. - 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 17.5–22.7) and 16.5 cm (13.3– 19.7) 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; 135.8– 144.8). 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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| 3. |
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| 4. |
- Danaei, Goodarz, et al.
(författare)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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| 5. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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| 6. |
- Arnold, Natalie, et al.
(författare)
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C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease : the BiomarCaRE project
- 2024
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 45:12, s. 1043-1054
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L).Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024).Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.
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| 7. |
- Arnold, Natalie, et al.
(författare)
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Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease
- 2024
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 84:2, s. 165-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities.Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events.Methods: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as “LDL-C—Lp(a)-C,” where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile).Results: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49).Conclusions: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.
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| 8. |
- Börschel, Christin S., et al.
(författare)
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Risk prediction of atrial fibrillation and its complications in the community using hs troponin I
- 2023
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Ingår i: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 53:5
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood-based biomarkers reflecting cardiac injury such as high-sensitivity troponin I (hsTnI) may help close this gap.Methods: We investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C-reactive protein, N-terminal pro B-type natriuretic peptide).Results: During a median follow-up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91-fold (95% confidence interval (CI) 3.30, 4.63; p <.01) risk for developing AF compared to the lowest quarter (<1.4 ng/L). In multivariable-adjusted Cox proportional hazards models a statistically significant association was seen between hsTnI and AF (hazard ratio (HR) per 1 standard deviation (SD) increase in log10(hsTnI) 1.08; 95% CI 1.01, 1.16; p =.03). Inclusion of hsTnI did improve model discrimination (C-index CVRF 0.811 vs. C-index CVRF and hsTnI 0.813; p <.01). Higher hsTnI concentrations were associated with heart failure (HR per SD 1.37; 95% CI 1.12, 1.68; p <.01) and overall mortality (HR per SD 1.24; 95% CI 1.09, 1.41; p <.01).Conclusion: hsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRF and NT-proBNP. However, it is associated with the AF-related disease heart failure and mortality likely reflecting underlying subclinical cardiovascular impairment.
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| 9. |
- Camen, Stephan, et al.
(författare)
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Cardiac Troponin I and Incident Stroke in European Cohorts : Insights From the BiomarCaRE Project
- 2020
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 51:9, s. 2770-2777
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce.Methods: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries.Results: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021).Conclusions: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.
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| 10. |
- Camen, Stephan, et al.
(författare)
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Risk Factors, Subsequent Disease Onset, and Prognostic Impact of Myocardial Infarction and Atrial Fibrillation
- 2022
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood.METHODS AND RESULTS: In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all-cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population-based cohorts. During a maximum follow-up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03–2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31–2.34) both significantly increased overall mortality risk.CONCLUSIONS: We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.
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| 11. |
- Camen, Stephan, et al.
(författare)
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Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality
- 2020
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 22:4, s. 522-529
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Tidskriftsartikel (refereegranskat)abstract
- Aims Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. Methods and results Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001). Conclusion The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.
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| 12. |
- Cameron, Adrian J., et al.
(författare)
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Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults
- 2020
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 9:13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated.Methods and Results: The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex‐specific Cox models, stratified by cohort, with age as the time scale. Models included baseline categorical obesity measures, age, total and high‐density lipoprotein cholesterol, systolic blood pressure, antihypertensive drugs, smoking, and diabetes mellitus. A total of 9105 all‐cause deaths were recorded during a median follow‐up of 10 years. Hazard ratios for all‐cause death presented J‐ or U‐shaped associations with most obesity measures. With waist and hip circumference included in the same model, for all hip sizes, having a smaller waist was strongly associated with lower risk of death, except for men with the smallest hips. In addition, among those with smaller waists, hip size was strongly negatively associated with risk of death, with ≈20% more people identified as being at increased risk compared with waist circumference alone.Conclusions: A more complex relationship between hip circumference, waist circumference, and risk of death is revealed when both measures are considered simultaneously. This is particularly true for individuals with smaller waists, where having larger hips was protective. Considering both waist and hip circumference in the clinical setting could help to best identify those at increased risk of death.
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| 13. |
- Csengeri, Dora, et al.
(författare)
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Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:12, s. 1170-1177
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts.METHODS AND RESULTS: In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11-1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF.CONCLUSIONS: In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention.
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| 14. |
- Gianfagna, Francesco, et al.
(författare)
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The role of neuromedin U in adiposity regulation. Haplotype analysis in European children from the IDEFICS Cohort.
- 2017
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Neuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children.From a large European multi-center study on childhood obesity, 4,528 children (2.0-9.9 years, mean age 6.0±1.8 SD; boys 52.2%) were randomly selected, stratifying by age, sex and country, and genotyped for tag single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653,C:T) of NMU gene, then haplotypes were inferred. Regression models were applied to estimate the associations between SNPs or haplotypes and BMI as well as other anthropometric measures. BMI was associated with all NMU SNPs (p<0.05). Among five haplotypes inferred, the haplotype carrying the minor alleles (CCT, frequency = 22.3%) was the only associated with lower BMI values (beta = -0.16, 95%CI:-0.28,-0.04, p = 0.006; z-score, beta = -0.08, 95%CI:-0.14,-0.01, p = 0.019) and decreased risk of overweight/obesity (OR = 0.81, 95%CI:0.68,0.97, p = 0.020) when compared to the most prevalent haplotype (codominant model). Similar significant associations were also observed using the same variables collected after two years' time (BMI, beta = -0.25, 95%CI:-0.41,-0.08, p = 0.004; z-score, beta = -0.10, 95%CI:-0.18,-0.03, p = 0.009; overweight/obesity OR = 0.81, 95%CI:0.66,0.99, p = 0.036). The association was age-dependent in girls (interaction between CCT haplotypes and age, p = 0.008), more evident between 7 and 9 years of age. The CCT haplotype was consistently associated with lower levels of fat mass, skinfold thickness, hip and arm circumferences both at T0 and at T1, after adjustment for multiple testing (FDR-adjusted p<0.05).This study shows an association between a NMU haplotype and anthropometric indices, mainly linked to fat mass, which appears to be age- and sex-specific in children. Genetic variations within or in linkage with this haplotype should be investigated to identify functional variants responsible for the observed phenotypic variation.
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| 15. |
- Gianfagna, Francesco, et al.
(författare)
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Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children.
- 2013
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2±1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δ=-1.8, p=0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0-43.9%), the CCT haplotype (frequency=39.7%) was associated with lower SI values (dominant model, Δ=-1.0, p=0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequency=8.4%) showed much lower SI than non-carriers (Δ=-3.9, p<0.0001; p for interaction=0.025). The association was more evident in preschool girls, in whom SI showed a curvilinear trend across ages. In subgroup analyses, rs9999653 CC NMU or both GG ADRB2 genotypes were associated with either lower serum calcium or β-CrossLaps levels (p=0.01). This study in European children shows, for the first time in humans, a role for NMU gene through interaction with ADRB2 gene in bone strength regulation, more evident in preschool girls.
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| 16. |
- Grippi, Claudio, et al.
(författare)
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Association between variants of neuromedin U gene and taste thresholds and food preferences in European children: Results from the IDEFICS study.
- 2019
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Ingår i: Appetite. - : Elsevier BV. - 1095-8304 .- 0195-6663. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide neuromedin U (NMU) known for its role in appetite, feeding and energy balance could be involved in the control of food choice and taste sensitivity. We examined the association between NMU polymorphisms/haplotypes and taste thresholds and food preferences in a population of European children.A total of 578 subjects from the IDEFICS study (mean age 7.5±0.8 SD, boys 53.6%) with NMU genotype data and food preference (salty, fatty, sweet, flavour and umami food) and taste threshold (salt, fat, sweet, umami) tests available were analysed. Three single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653, C:T) of NMU gene were analyzed and five major haplotypes were inferred. The associations between genotypes and food preferences or taste thresholds were investigated (odds ratios -OR, adjusted for age, sex and country). A p<0.05 after false discovery rate adjustment (pFDR) was considered statistically significant.The association between NMU genotypes and food preference showed two NMU SNPs associated with preference for food containing sodium glutamate (umami taste; rs6827359C, OR=1.61, 95% confidence interval (CI):1.20-2.17; rs9999653T, OR=1.59, 95%CI:1.18-2.13). In the haplotype analysis, the CTT haplotype showed an OR of 1.70 (95%CI:1.16-2.5) for the umami food preference, while CCT haplotype showed an OR of 1.63 (95%CI:1.11-2.40), compared to the most frequent haplotype (TTC). Carriers of CCT/CCT vs subjects with no CCT haplotype showed an OR of 4.78 (95%CI:1.86-12.30). Umami food preference was associated with low values of BMI z-score, arm circumferences, skinfolds and fat mass (pFDR<0.05). No association between NMU genetic variants and taste thresholds was found.This study shows for the first time in children an association between preference for umami food and a NMU haplotype, previously found associated with low BMI values.
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| 17. |
- Hägg, Sara, et al.
(författare)
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Adiposity as a cause of cardiovascular disease : a Mendelian randomization study
- 2015
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 578-586
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods. Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes. Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (beta = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD. Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.
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| 18. |
- Jilani, Hannah, et al.
(författare)
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Correlates of bitter, sweet, salty and umami taste sensitivity in European children: Role of sex, age and weight status - The IDEFICS study
- 2022
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Ingår i: Appetite. - : Elsevier BV. - 0195-6663 .- 1095-8304. ; 175
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to describe differences in taste sensitivity in children according to age across 7- to 11-year-old children from eight European countries. We further compared taste sensitivity between boys vs. girls and under-/normal weight vs. overweight/obese children. Within the European multicentre IDEFICS (Identification and prevention of dietary and lifestyle-induced health effects in children and infants) study, 1938 school children participated in sweet, bitter, salty and umami detection threshold tests between 2007 and 2010, using the paired comparison staircase method. The lowest concentration at which the child was able to detect a difference to water was determined as taste detection threshold as a proxy of taste sensitivity. Mean taste thresholds were calculated stratified for sex, age groups, weight groups and country. BMI was calculated using measured height and weight; socio-demographic information was collected using questionnaires. Ordinal logistic regressions were conducted to investigate the association between sex, weight status (as categorical exposure variable) and age (as continuous exposure variable) and the taste sensitivity for the four taste modalities (as outcome), separately. Older children were more taste sensitive for sweet and salty and less taste sensitive for umami and bitter than younger children. Girls were more sensitive to sweet taste than boys. Overweight or obese children were less sensitive to sweet and salty taste compared to normal weight children This was the first study comparing taste sensitivity by measuring taste thresholds in children across different European countries. We conclude that taste thresholds are associated with weight status, children become more sensitive to sweet and salty tastes with increasing age, and girls might be more sensitive to sweet than boys.
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| 19. |
- Magnussen, Christina, et al.
(författare)
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Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe)
- 2017
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 136:17, s. 1588-1597
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood.Methods: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1–97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years.Results: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12–1.23 in women versus 1.31; 95% CI 1.25–1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81–0.90 versus 0.92; 95% CI, 0.88–0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index.Conclusions: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies.
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| 20. |
- Magnussen, Christina, et al.
(författare)
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Sex-Specific Epidemiology of Heart Failure Risk and Mortality in Europe Results From the BiomarCaRE Consortium
- 2019
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Ingår i: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 7:3, s. 204-213
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES This study investigates differences between women and men in heart failure (HF) risk and mortality. BACKGROUND Sex differences in HF epidemiology are insufficiently understood. METHODS In 78,657 individuals (median 49.5 years of age; age range 24.1 to 98.7 years; 51.7% women) from community-based European studies (FINRISK, DanMONICA, Moli-sani, Northern Sweden) of the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium, the association between incident HF and mortality, the relationship of cardiovascular risk factors, prevalent cardiovascular diseases, biomarkers (C-reactive protein [CRP]; N-terminal pro-B-type natriuretic peptide [NT-proBNP]) with incident HF, and their attributable risks were tested in women vs. men. RESULTS Over a median follow-up of 12.7 years, fewer HF cases were observed in women (n = 2,399 [5.9%]) than in men (n = 2,771 [7.3%]). HF incidence increased markedly after 60 years of age, initially with a more rapid increase in men, whereas incidence in women exceeded that of men after 85 years of age. HF onset substantially increased mortality risk in both sexes. Multivariable-adjusted Cox models showed the following sex differences for the association with incident HF: systolic blood pressure hazard ratio (HR) according to SD in women of 1.09 (95% confidence interval [CI]: 1.05 to 1.14) versus HR of 1.19 (95% CI: 1.14 to 1.24) in men; heart rate HR of 0.98 (95% CI: 0.93 to 1.03) in women versus HR of 1.09 (95% CI: 1.04 to 1.13) in men; CRP HR of 1.10 (95% CI: 1.00 to 1.20) in women versus HR of 1.32 (95% CI: 1.24 to 1.41) in men; and NT-proBNP HR of 1.54 (95% CI: 1.37 to 1.74) in women versus HR of 1.89 (95% CI: 1.75 to 2.05) in men. Population-attributable risk of all risk factors combined was 59.0% in women and 62.9% in men. CONCLUSIONS Women had a lower risk for HF than men. Sex differences were seen for systolic blood pressure, heart rate, CRP, and NT-proBNP, with a lower HF risk in women.
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| 21. |
- Schrage, Benedikt, et al.
(författare)
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Comparison of Cardiovascular Risk Factors in European Population Cohorts for Predicting Atrial Fibrillation and Heart Failure, Their Subsequent Onset, and Death
- 2020
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in risk factors for atrial fibrillation (AF) and heart failure (HF) are incompletely understood. Aim of this study was to understand whether risk factors and biomarkers show different associations with incident AF and HF and to investigate predictors of subsequent onset and mortality.Methods and Results: In N=58 693 individuals free of AF/HF from 5 population-based European cohorts, Cox regressions were used to find predictors for AF, HF, subsequent onset, and mortality. Differences between associations were estimated using bootstrapping. Median follow-up time was 13.8 years, with a mortality of 15.7%. AF and HF occurred in 5.0% and 5.4% of the participants, respectively, with 1.8% showing subsequent onset. Age, male sex, myocardial infarction, body mass index, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) showed similar associations with both diseases. Antihypertensive medication and smoking were stronger predictors of HF than AF. Cholesterol, diabetes mellitus, and hsCRP (high-sensitivity C-reactive protein) were associated with HF, but not with AF. No variable was exclusively associated with AF. Population-attributable risks were higher for HF (75.6%) than for AF (30.9%). Age, male sex, body mass index, diabetes mellitus, and NT-proBNP were associated with subsequent onset, which was associated with the highest all-cause mortality risk.Conclusions: Common risk factors and biomarkers showed different associations with AF and HF, and explained a higher proportion of HF than AF risk. As the subsequent onset of both diseases was strongly associated with mortality, prevention needs to be rigorously addressed and remains challenging, as conventional risk factors explained o:nly 31% of AF risk.
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| 22. |
- Scott, Robert A., et al.
(författare)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 23. |
- Toprak, Betül, et al.
(författare)
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Exploring the incremental utility of circulating biomarkers for robust risk prediction of incident atrial fibrillation in European cohorts using regressions and modern machine learning methods
- 2023
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:3, s. 812-819
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables.Methods and results: In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82-2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13-1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10-1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02-1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index.Conclusion: Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively.
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