| 1. |
- Frej, Fyhrquist, et al.
(author)
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Telomere Biology and Vascular Aging
- 2015
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In: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128016763 - 9780128013878 ; , s. 201-211
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Book chapter (peer-reviewed)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. |
- Nilsson, Peter M., et al.
(author)
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Early Vascular Aging in the Young : Influence of Birth Weight and Prematurity
- 2015
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In: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128016763 - 9780128013878 ; , s. 129-136
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Book chapter (peer-reviewed)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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| 3. |
- Nilsson, Peter M., et al.
(author)
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Preface
- 2015
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In: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128013878 - 9780128016763
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Book chapter (other academic/artistic)
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| 4. |
- Nilsson, Peter M., et al.
(author)
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Preface
- 2015
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In: Early Vascular Aging (EVA) : New Directions in Cardiovascular Protection - New Directions in Cardiovascular Protection. - 9780128013878 - 9780128016763
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Book chapter (other academic/artistic)
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| 5. |
- Nilsson, Peter, et al.
(author)
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The enigma of increased non-cancer mortality after weight loss in healthy men who are overweight or obese.
- 2002
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 252:1, s. 70-78
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Journal article (peer-reviewed)abstract
- Objective. To study effects on non-cancer mortality of observational weight loss in middle-aged men stratified for body mass index (BMI), taking a wide range of possible confounders into account. Design. Prospective, population based study. Setting. Male population of Malmö, Sweden. Participants. In all 5722 men were screened twice with a mean time interval of 6 years in Malmö, southern Sweden. They were classified according to BMI category at baseline (<21, 22-25, overweight: 26-30, and obesity: 30+ kg m-2) and weight change category until second screening (weight stable men defined as having a baseline BMI ± 0.1 kg m-2 year-1 at follow-up re-screening). Main outcome measures. Non-cancer mortality calculated from national registers during 16 years of follow-up after the second screening. Data from the first year of follow-up were excluded to avoid bias by mortality caused by subclinical disease at re-screening. Results. The relative risk (RR; 95% CI) for non-cancer mortality during follow-up was higher in men with decreasing BMI in all subgroups: RR 2.64 (1.46-4.71, baseline BMI <21 kg m-2), 1.39 (0.98-1.95, baseline BMI 22-25 kg m-2), and 1.71 (1.18-2.47, baseline BMI 26+ kg m-2), using BMI-stable men as reference group. Correspondingly, the non-cancer mortality was also higher in men with increasing BMI, but only in the obese group (baseline BMI 26+ kg m-2) with RR 1.86 (1.31-2.65). In a subanalysis, nonsmoking obese (30+ kg m-2) men with decreased BMI had an increased non-cancer mortality compared with BMI-stable obese men (Fischer's test: P=0.001). The mortality risk for nonsmoking overweight men who increased their BMI compared with BMI-stable men was also significant (P=0.006), but not in corresponding obese men (P=0.094). Conclusions. Weight loss in self-reported healthy but overweight middle-aged men, without serious disease, is associated with an increased non-cancer mortality, which seems even more pronounced in obese, nonsmoking men, as compared with corresponding but weight-stable men. The explanation for these observational findings is still enigmatic but could hypothetically be because of premature ageing effects causing so-called weight loss of involution.
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| 6. |
- Borgquist, Rasmus, et al.
(author)
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Coronary flow velocity reserve reduction is comparable in patients with erectile dysfunction and in patients with impaired fasting glucose or well-regulated diabetes mellitus
- 2007
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In: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8275. ; 14:2, s. 258-264
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Journal article (peer-reviewed)abstract
- Background There is growing evidence that erectile dysfunction is a sentinel for future coronary artery disease. Recently published studies have shown signs of impaired coronary endothelial function in patients with erectile dysfunction, without clinical cardiovascular disease and diabetes. We evaluated the magnitude of coronary vasodilatory dysfunction in men with erectile dysfunction, as compared with men with impaired glucose metabolism (impaired fasting glucose or diabetes) and healthy controls. Methods We investigated men aged 68-73 years with erectile dysfunction (n=12), age-matched men with impaired glucose metabolism, who all proved to have erectile dysfunction (n=15), and age-matched male controls (n=12). Erectile dysfunction was evaluated using the International Index of Erectile Function (IIEF)-5 questionnaire. Coronary flow velocity reserve in the left anterior descending artery was examined using Doppler ultrasound and intravenous adenosine provocation. Results Coronary flow velocities at rest did not differ between the three groups, but maximum coronary flow velocity was significantly lower in the erectile dysfunction group (P= 0.004) and in the impaired glucose metabolism group (P= 0.019), as compared with controls. There was no difference between the erectile dysfunction and impaired glucose metabolism groups. Coronary flow velocity reserve was reduced in the erectile dysfunction group (P=0.026) compared to controls, but was similar compared to the impaired glucose metabolism group. In multivariate analysis including all groups, erectile dysfunction score was the only independent predictor of reduced coronary flow velocity reserve (P=0.020). Conclusions The magnitude of early coronary endothelial and smooth muscle cell dysfunction in otherwise healthy men with erectile dysfunction was comparable to that of patients with impaired glucose metabolism: a well known risk factor for coronary artery disease.
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| 7. |
- Folkersen, Lasse, et al.
(author)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Journal article (peer-reviewed)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 8. |
- Molvin, John, et al.
(author)
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Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip.
- 2020
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In: Open heart. - : BMJ. - 2053-3624 .- 2398-595X. ; 7:1
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Journal article (peer-reviewed)abstract
- Atrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity and mortality. Its increasing prevalence calls for novel biomarkers to identify underlying pathophysiological mechanisms as well as patients at risk.Plasma samples from 1694 individuals from the Swedish population-based Malmö Preventive Project (mean age 69.5 years; 29.3% female; mean follow-up time 9.7±3.1 years) were analysed with the Olink proximity extension assay CVD III panel consisting of 92 proteins to identify proteins associated with incident AF or atrial flutter, referred to as incident AF. Incident cases of AF (n=278) were retrieved by linkage to the registers. Participants were followed until the first episode of AF or until censoring by death or emigration. Bonferroni-corrected multivariable Cox regression models adjusted for known risk factors were used to explore possible associations of the 92 proteins and incidence of AF.Multivariable Cox regression analyses of 11 proteins associated with incident AF (mean follow-up time 9.7±3.1 years) after Bonferroni correction confirmed N-terminal pro-B-type natriuretic peptide (HR per 1 SD increment (95% CI) 1.80 (1.58 to 2.04); p=1.2×10-19) as risk marker of incident AF. Further, matrix metalloproteinase-2 (1.22 (1.07 to 1.39); p=0.002) and osteopontin (1.27 (1.12 to 1.44); p=2.7×10-4) were associated with incident AF at follow-up independently of traditional risk markers and NT-proBNP.In a general Swedish population, we confirmed the well-known association of NT-proBNP with incident AF and also identified matrix metalloproteinase-2 and osteopontin as novel risk markers for incident AF, independently of traditional risk factors and NT-proBNP.
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| 9. |
- Pennells, Lisa, et al.
(author)
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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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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Journal article (peer-reviewed)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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