| 1. |
- Brunkwall, Louise, et al.
(författare)
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The Malmö Offspring Study (MOS) : design, methods and first results.
- 2021
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 36, s. 103-116
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Tidskriftsartikel (refereegranskat)abstract
- As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.
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| 2. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Bladh, Magnus, et al.
(författare)
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Defined shapes of carotid artery calcifications on panoramic radiographs correlate with specific signs of cardiovascular disease on ultrasound examination
- 2024
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Ingår i: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. - : Elsevier. - 2212-4403 .- 2212-4411.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to optimize diagnostics for carotid artery calcifications (CACs) on panoramic radiographs (PRs) to identify cardiovascular disease (CVD) by investigating how 4 defined CAC shapes are associated with ultrasound (US) findings indicating CVD. Study Design: The study included 414 participants (802 neck sides) from the Malmö Offspring Dental Study, examined with PRs. The PRs were assessed for CAC shapes stratified into 4 categories: single, scattered, vessel-width defining, and vessel-outlining. The carotid arteries were examined with US for signs of CVD: the presence of plaques, largest individual area of a plaque, number of plaques, and percentage reduction of the lumen. Associations between the different CAC categories and US characteristics were analyzed. Results: All categories of CAC were significantly associated with a higher degree of US findings indicating CVD compared with no CAC (P < .001). The most significant differences were found for vessel-outlining CAC, with the mean of the largest individual plaque area of 17.9 vs 2.3 mm2, mean number of plaques 1.6 vs 0.2, and mean percentage reduction of the lumen 24.1% vs 3.5% (all P < .001). Conclusions: Independent of shape, CACs detected on PRs were associated with a higher degree of US findings of CVD. This was most pronounced for vessel-outlining CAC. With refined differential diagnostics of CACs in PRs, dentists may contribute to improved identification of patients in need of cardiovascular prevention.
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| 4. |
- Holm Isholth, Hannes, et al.
(författare)
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The impact of prediabetes and diabetes on endothelial function in a large population-based cohort
- 2024
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Ingår i: Blood Pressure. - 0803-7051. ; 33:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiabetes and prediabetes are well-recognized risk factors for cardiovascular disease (CVD) and are marked by vascular endothelial dysfunction (ED). However, there is a scarcity of thorough population-based studies examining ED in individuals with diabetes/prediabetes free from manifest CVD. Here, we examined the association between ED assessed by reactive hyperaemia index (RHI) in the finger and diabetes/prediabetes in a large middle-aged population cohort.MethodsWithin the Malmö Offspring Study, following the exclusion of participants <30 years and participants with prevalent CVD, 1384 participants had complete data on all covariates. The RHI was calculated using pulse amplitude tonometry. ED was defined as RHI < 1.67. Multivariable logistic and linear regression models were conducted to investigate associations between ED and RHI with diabetes and prediabetes.ResultsThe study population had a mean age of 53.6 ± 7.6 years (53% women). In study participants with manifest diabetes (n = 121) and prediabetes (n = 514), ED was present in 42% and 25% respectively, compared to 23% in those with normal glucometabolic status. In multivariable logistic regression analyses, prevalent diabetes was significantly associated with ED (OR 1.95; 95%CI 1.57-3.39; p = 0.002), as well as with lower RHI (β-coeff. -0.087; p = 0.002). However, prediabetes showed no association with neither ED nor RHI.ConclusionIn a population free from CVD, vascular endothelial dysfunction was primarily associated with manifest diabetes, but not with prediabetes, implying that finger ED may develop when diabetes is established, rather than being an early sign of glucose intolerance. Further research is needed to explore whether addressing glucose intolerance could potentially delay or prevent vascular ED onset.
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| 5. |
- Muhammad, Iram Faqir, et al.
(författare)
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Acute phase proteins as prospective risk markers for arterial stiffness : The Malmö Diet and Cancer cohort
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Arterial stiffness plays a significant role in the development and progression of adverse cardiovascular events and all-cause mortality. This observational study aims to explore the relationship between six acute phase proteins namely, ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin, complement C3 and C-reactive protein (CRP), and carotid-femoral pulse wave velocity (c-f PWV) in a population-based cohort, and to also explore the effect of low-grade inflammation on the relationship between diabetes and c-f PWV. Method: The study consisted of participants from the Malmö Diet and Cancer study with data from baseline examinations (1991–1994) and follow-up examinations (2007–2012). Arterial stiffness was measured at follow-up by determining c-f PWV. After excluding participants with missing data, the total study population included 2338 subjects. General linear models were used to assess the relationship between baseline acute phase proteins and c-f PWV. Results: After adjusting for traditional risk factors the participants in the 4th quartile vs 1st quartile of alpha-1-antitrypsin (geometric mean: 10.32 m/s vs 10.04 m/s) (<0.05), C3 (10.35 m/s vs 10.06 m/s) (p<0.05) and CRP (10.37 m/s vs 9.96 m/s) (<0.001) showed significant association with c-f PWV. Diabetes at follow-up was also associated with high c-f PWV, however, this relationship was independent of low grade inflammation. Conclusion: Alpha-1-antitrypsin, C3 and CRP are associated with arterial stiffness. The results indicate that low grade inflammation is associated with arterial stiffness in addition to established cardiovascular risk factors.
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| 6. |
- Muhammad, Iram Faqir, et al.
(författare)
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Arterial stiffness and incidence of diabetes : A population-based cohort study
- 2017
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:12, s. 1739-1745
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Diabetes is known to be associated with increased arterial stiffness. However, the temporal association between increased carotid-femoral pulse wave velocity (c-f PWV) and diabetes is unclear. The aim of this study is to explore the relationship between arterial stiffness, as determined by c-f PWV, and incidence of diabetes. Research Design and Methods: The study population included participants from the Malmö Diet and Cancer cardiovascular cohort, using measurements from the 2007-2012 reexamination as baseline. Arterial stiffness was evaluated by measuring c-f PWV (SphygmoCor). After excluding participants with prevalent diabetes (according to measurements of fasting glucose, oral glucose tolerance tests, and physician's diagnoses), the final study population consisted of 2,450 individuals (mean age = 71.965.6 years). Incidence of diabetes was followed by linkage to local and national diabetes registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to the tertiles of c-f PWV, adjusted for potential confounders. Results: During a mean follow-up of 4.43 6 1.40 years, 68 (2.8%) participants developed diabetes. Crude incidence of diabetes (per 1,000 person-years) was 3.5, 5.7, and 9.5, respectively, for subjects in the first, second, and third tertiles of c-f PWV. After adjustment for potential confounders, the hazard ratio of diabetes was 1.00 (reference), 1.83 (95% CI 0.88-3.8), and 3.24 (95% CI 1.51-6.97), respectively, for the tertiles of c-f PWV (P for trend = 0.002). Conclusions: Increased c-fPWV is associated with increased incidence of diabetes, independent of other risk factors. These results suggest that increased arterial stiffness is an early risk marker for developing diabetes.
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| 9. |
- Ottosson, Filip, et al.
(författare)
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The inverse association between a fish consumption biomarker and gingival inflammation and periodontitis : A population-based study
- 2022
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 49:4, s. 353-361
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is a fatty fish–intake biomarker. We investigated the association between plasma levels of CMPF in relation to gingival inflammation and periodontitis case definition, as well as the extent and severity variables. Materials and Methods: The Malmö Offspring Study is a population-based study, and the Malmö Offspring Dental Study (MODS) is its dental arm, including periodontal charting. Plasma CMPF was measured using liquid chromatography–mass spectrometry and studied in relation to periodontal diagnosis and parameters using multivariable linear or logistic regression modelling adjusting for age, sex, education, body mass index, fasting glucose, and smoking. Results: Metabolite data were available for 922 MODS participants. Higher CMPF levels were associated with less gingival inflammation (β = −2.12, p =.002) and lower odds of severe periodontitis (odds ratio [OR] = 0.74, 95% confidence interval [CI]: 0.56 to 0.98). Higher CMPF levels were also associated with more teeth (β = 0.19, p =.001), lower number of periodontal pockets (≥4 mm) (β = −1.07, p =.007), and lower odds of having two or more periodontal pockets of ≥6 mm (OR = 0.80, 95% CI: 0.65 to 0.98) in fully adjusted models. Conclusions: CMPF, a validated biomarker of fatty fish consumption, is associated with less periodontal inflammation and periodontitis. Residual confounding cannot be ruled out, and future studies are warranted.
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| 10. |
- 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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