| 1. |
- Frej, Fyhrquist, et al.
(författare)
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Telomere Biology and Vascular Aging
- 2015
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Ingår i: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128016763 - 9780128013878 ; , s. 201-211
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Bokkapitel (refereegranskat)abstract
- Telomeres form the end segment of the DNA helix and shorten with every cell division until getting so short that the cell stops dividing and will undergo programmed cell death (apoptosis). Research has supported the view that telomere length could be regarded as a marker of biological aging, even if methodological problems could interfere with the interpretation of telomere length in cross-sectional studies when causality cannot be proven. Ideally the telomere attrition rate should be calculated based on repeated measurements during follow-up. So far, epidemiological studies have supported the role of short telomeres being predictive of coronary heart disease (CHD) events but not stroke, based on meta-analysis. A genetic risk score based on several genetic markers of telomere biology is associated with CHD risk, which proves that a true causal and unconfounded relationship may exist. Future intervention studies will hopefully reveal whether telomere length is possible to influence by lifestyle improvements or drug therapy in randomized, controlled studies.
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| 2. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 3. |
- Nilsson, Peter M., et al.
(författare)
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Early Vascular Aging in the Young : Influence of Birth Weight and Prematurity
- 2015
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Ingår i: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128016763 - 9780128013878 ; , s. 129-136
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Bokkapitel (refereegranskat)abstract
- Longitudinal data from cohort studies show that early life factors such as low birth weight are associated with the development of hypertension, coronary heart disease, and type 2 diabetes in adulthood. Moreover, the majority of published studies concur that blood pressure is higher in adolescents and young adults with a history of low birth weight. Although the precise mechanisms linking early life factors with increased future cardiovascular risk are unclear, the architecture of the vascular system is programmed in utero and the majority of elastin, the major structural component underlying arterial wall elasticity, is synthesized and deposited during this time. Therefore, the arterial system has been a major focus of investigations aimed toward improving our understanding of the natural history of hypertension and future cardiovascular risk. A number of studies have now described properties relating to arterial structure and function in children, adolescents, and young adults, with a history of low birth weight, due to being either small for gestational age or premature. While the combination of prematurity and intrauterine growth retardation resulting in a small for gestational age phenotype appears to be associated with the most marked impairments in vascular structure and function, the small for gestational age phenotype, followed by a rapid "catch-up" growth also appears harmful. Further studies are needed to understand the long-term consequences of cardiovascular health of being born under adverse conditions, especially when post-natal growth trajectories are taken into account.
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| 4. |
- Nilsson, Peter M., et al.
(författare)
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Preface
- 2015
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Ingår i: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128013878 - 9780128016763
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Nilsson, Peter M., et al.
(författare)
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Preface
- 2015
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Ingår i: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128013878 - 9780128016763
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
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| 7. |
- Song, Xin, et al.
(författare)
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Obesity attenuates gender differences in cardiovascular mortality
- 2014
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 13, s. 144-
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Tidskriftsartikel (refereegranskat)abstract
- Background: To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender. Methods: Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale. Results: Men had higher CVD mortality than women in all four BMI categories (<25.0, 25.0-29.9, 30.0-34.9 and >= 35.0 kg/m(2)). Compared with the lowest BMI category in women, multivariable adjusted HRs (95% confidence intervals) for higher BMI categories are 1.0 (0.8-1.4), 1.6 (1.1-2.1) and 2.8 (2.0-3.8) in women and 2.8 (2.2-3.6), 3.1 (2.5-3.9), 3.8 (2.9-4.9) and 5.4 (3.8-7.7) in men, respectively. Similar findings were observed for abdominal obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals. Conclusions: Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.
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| 8. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 9. |
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| 10. |
- 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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