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1.	Bergström, Göran, 1964, et al. (författare) Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS. 2023 Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54 Tidskriftsartikel (refereegranskat)abstract Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
2.	Engström, Gunnar, et al. (författare) The Swedish CArdioPulmonary BioImage Study : objectives and design 2015 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659 Tidskriftsartikel (refereegranskat)abstract Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
3.	Ekblom, Örjan, 1971-, et al. (författare) Concurrent and predictive validity of physical activity measurement items commonly used in clinical settings- data from SCAPIS pilot study 2015 Ingår i: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: As the understanding of how different aspects of the physical activity (PA) pattern relate to health and disease, proper assessment is increasingly important. In clinical care, self-reports are the most commonly used assessment technique. However, systematic comparisons between questions regarding concurrent or criterion validity are rare, as are measures of predictive validity. The aim of the study was to examine the concurrent (using accelerometry as reference) and predictive validity (for metabolic syndrome) of five PA questions. Methods: A sample of 948 middle-aged Swedish men and women reported their PA patterns via five different questions and wore an accelerometer (Actigraph GT3X) for a minimum of 4 days. Concurrent validity was assessed as correlations and ROC-analyses. Predictive validity was assessed using logistic regression, controlling for potential confounders. Results: Concurrent validity was low-to-moderate (r < 0.35 and ROC AUC < 0.7) with large misclassifications regarding time spent sitting/sedentary and in moderate-to vigorous PA. The predictive validity of the questions was good, and one question (PHAS) showed an 80 % decreased odds-ratio of having metabolic syndrome, after taking potential confounders into consideration. Discussion: In this mixed sample of adults, both concurrent and predictive validity vaired between items and between measures of the physical activity pattern. The PHAS and WALK items are proposed for assessment of adherence to PA recommendations. Conclusion: Assessing PA patterns using self-report measures results in methodological problems when trying to predict individual risk for the metabolic syndrome, as the concurrent validity generally was low. However, several of the investigated questions may be useful for assessing risk at a group level, showing better predictive validity.
4.	Engström, Gunnar, et al. (författare) Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications 2024 Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49 Tidskriftsartikel (refereegranskat)abstract Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
5.	Agewall, S, et al. (författare) Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up 2001 Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 249:1, s. 305-314 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: The objective was to analyse whether a favourable change in risk factors, caused by a comprehensive risk factor modification programme, affected intima-media thickness (IMT) in the common carotid artery, and whether any such change was associated with a change in cardiovascular events during a 6-year follow-up. DESIGN: Patients were randomized 1 : 1 to special intervention or usual care. SETTING: Hypertension Unit at university hospital. SUBJECTS: A total of 164 patients were randomized. Inclusion criteria were male, aged 50-72 years (at randomization) and one or more of the following: Serum cholesterol level > 6.5 mmol L(-1), smoking or diabetes mellitus. All patients were prescribed antihypertensive treatment since many years. In 142 men good quality ultrasound recording of the common carotid IMT were achieved at baseline, 119 were re-examined after 3.3 years, and 97 patients were available for examination after mean follow-up time of 6.2 years. Cardiovascular events were available for all randomized patients. INTERVENTIONS: The nonpharmacological special intervention programme was based on one information meeting followed by five weekly 2-h sessions with participation of patients and spouses. The diet recommendations were similar to established guidelines. Overweight patients were instructed to lose weight, and diabetic patients were systematically taught self-monitoring of blood glucose. Smokers were invited to a smoking cessation programme with five weekly meetings. Follow-up visits were thereafter scheduled every 6 months. Lipid lowering drugs were recommended in the intervention group if the treatment goals using nonpharmacological measures were not achieved. Patients in the usual care group were told to quit smoking and to lower their consumption of fat and glucose. Antihypertensive treatment (i.e., selection of drugs) was on purpose kept similar in the two groups. MAIN OUTCOME MEASURES: The IMT of the common carotid artery as measured by ultrasound. Cardiovascular events during follow-up. RESULTS: Significant net reductions were seen for serum cholesterol, triglycerides, fasting glucose and smoking. No difference in change in IMT was observed during follow-up between the two randomization groups. The explanation was that patients with positive plaque status at baseline had a much larger increase in IMT over time than patients with negative plaque status, and that patients with positive plaque status more often survived and were available for re-examination after 6 years in the intervention group than in the usual care group. Total mortality was lower in the intervention group, compared with the usual care group, 13 and 29%, respectively (P=0.028). CONCLUSIONS: In high risk populations, long-term studies with surrogate endpoints may be misleading because of missing data in patients where a large increase in IMT would have been observed, had they been re-examined. Another important conclusion from our study was that the gloomy prognosis for this patient category may be improved by a dedicated risk factor intervention programme. The improved prognosis was observed mainly in those patients at highest risk judged from history of cardiovascular disease or positive ultrasound plaque status at baseline.
6.	Amare, Azmeraw, et al. (författare) Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder. 2023 Ingår i: Research square. - : Research Square Platform LLC. Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<��.
7.	Amare, Azmeraw T, et al. (författare) Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. 2023 Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261 Tidskriftsartikel (refereegranskat)abstract Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
8.	Bahls, M., et al. (författare) Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium 2020 Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 27:3 Tidskriftsartikel (refereegranskat)abstract Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints. © The European Society of Cardiology 2019.
9.	Behre, Carl Johan, 1968, et al. (författare) Increasing Leisure Time Physical Activity is Associated With Less Prevalence of the Metabolic Syndrome in Healthy Middle-Aged Men 2011 Ingår i: Angiology. - : SAGE Publications. - 1940-1574 .- 0003-3197. Tidskriftsartikel (refereegranskat)abstract The metabolic syndrome (MetS) is characterized by a constellation of factors that confer an increased risk for cardiovascular morbidity and mortality. It is well-known that physical activity (PA) has a protective role on cardiovascular morbidity and mortality, mainly through its favorable effects on traditional risk factors such as body mass and blood pressure (BP). We assessed the prevalence of MetS in a population-based sample of 58-year-old men with respect to leisure-time PA and also to occupational PA. The results showed an inverse linear association (P < .05) between leisure time physical activity (LTPA) and MetS in this group. In conclusion, this study suggests that PA has an important role in controlling MetS.
10.	Behre, Carl Johan, 1968, et al. (författare) Moderate physical activity is associated with lower apoB/apoA-I ratio, independently of other risk factors in healthy middle-aged men. 2010 Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 61:8, s. 775-779 Tidskriftsartikel (refereegranskat)abstract Low-density lipoprotein is recognized as a primary vascular risk factor. However, recent data favor apolipoprotein (apo)B and apoA-I as risk factors with higher predictive values than conventional lipids. We investigated how leisure-time physical activity relates to the serum apoB/apoA-I ratio in middle-aged men. The results showed that compared with a sedentary lifestyle, moderate physical activity was associated with a decreased apoB/apoA-I ratio (1.01 ± 0.28 vs 0.87 ± 0.24, P < .05) and increased apoA-I levels (1.30 ± 0.20 g/L vs 1.43 ± 0.22 g/L, P < .05), whereas vigorous activity was required to observe a reduction in apoB levels (1.27 ± 0.28 g/L vs 1.14 ± 0.24 g/L, P < .05). A covariate analysis showed that leisure time physical activity was also associated with reduced apoB/apoA-I ratios after adjustment for smoking, systolic blood pressure and waist circumference. Importantly, this association was seen at moderate levels of physical activity, supporting the notion that some activity is better than none.
11.	Bergström, Göran, 1964, et al. (författare) Increased Leisure-Time Physical Activity is Associated With Lower Prevalence of the Metabolic Syndrome in 64-Year Old Women With Impaired Glucose Tolerance. 2012 Ingår i: Angiology. - : SAGE Publications. - 1940-1574 .- 0003-3197. ; 63:4, s. 297-301 Tidskriftsartikel (refereegranskat)abstract The metabolic syndrome (MetS) is characterized by a cluster of factors that confer an increased risk of cardiovascular morbidity as well as mortality. It is established that physical activity (PA) has a protective role in cardiovascular morbidity and mortality, mainly through favorable effects on traditional risk factors such as body mass and blood pressure. We assessed the prevalence of MetS in a population-based sample of 64-year-old women with impaired glucose tolerance (IGT) with respect to leisure-time PA (LTPA). The results showed an inverse linear association (P < .05) between LTPA and MetS in this group. In conclusion, this study suggests that an increased PA level has an important role in preventing MetS in women with IGT.
12.	Bergström, Göran, 1964, et al. (författare) Moderate Intensities of Leisure-Time Physical Activity Are Associated With Lower Levels of High-Sensitivity C-Reactive Protein in Healthy Middle-Aged Men. 2012 Ingår i: Angiology. - : SAGE Publications. - 1940-1574 .- 0003-3197. ; 63:6, s. 412-415 Tidskriftsartikel (refereegranskat)abstract Circulating C-reactive protein (CRP), reflective of systemic chronic low-grade inflammation, is a marker associated with cardiovascular disease (CVD). One of the mechanisms through which physical activity might promote cardiovascular health is by preventing changes in inflammation biomarkers, such as CRP. The present study examined the association of self-reported physical activity with an inflammation biomarker, high-sensitivity CRP (hs-CRP), in a population-based cohort of clinically healthy 58-year-old men. Compared with a sedentary lifestyle both moderate (1.81 [0.94-3.69] vs 1.28 [0.55-2.90] mg/L; P < .05) and vigorous physical activity (1.81 [0.94-3.69] vs 0.88 [0.42-1.81] mg/L; P < .001) were associated with decrease in hs-CRP levels. In summary, we identified an association between self-reported leisure time physical activity and hs-CRP in a cross-sectional study of healthy 58-year-old men, with decreased levels of CRP by increased intensities of physical activity.
13.	Bergström, Göran, 1964, et al. (författare) Self-efficacy regarding physical activity is superior to self-assessed activity level, in long-term prediction of cardiovascular events in middle-aged men 2015 Ingår i: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 15:820 Tidskriftsartikel (refereegranskat)abstract Background: Self-efficacy has been determined to be a strong predictor of who will engage in physical activity. We aimed to evaluate the associations between self-efficacy to perform physical activity, self-reported leisure-time physical activity and cardiovascular events in a population-based cohort of middle-aged Swedish men with no previous cardiovascular disease, or treatment with cardiovascular drugs. Methods: Analyses are based on 377 men randomly selected and stratified for weight and insulin sensitivity from a population sample of 58-year-old men (n = 1728) and who had answered a question about their competence to perform exercise (as an assessment of physical self-efficacy). The Saltin-Grimby Physical Activity Level Scale was used to assess self-reported levels of leisure-time physical activity. Cardiovascular events were recorded during 13-years of follow-up. Results: The group with poor self-efficacy to perform physical activity had a significantly higher incidence of cardiovascular events compared with the group with good physical self-efficacy (32.1 % vs 17.1 %, p < 0.01). Multivariate analyses showed that poor physical self-efficacy was associated with an increased relative risk of 2.0 (95 % CI 1.2 to 3.0), of having a cardiovascular event during follow-up also after adjustments for co-variates such as waist to hip ratio, heart rate, fasting plasma glucose, serum triglycerides, systolic blood pressure, apoB/apoA-I ratio and leisure-time physical activity. Conclusion: Self-efficacy to perform physical activity was strongly and independently associated with cardiovascular events and was superior to self-assessed physical activity in predicting cardiovascular events during 13-years of follow-up in a group of middle-aged men, without known CVD or treatment with cardiovascular drugs.
14.	Brohall, Gerhard, 1952, et al. (författare) Association between impaired glucose tolerance and carotid atherosclerosis: A study in 64-year-old women and a meta-analysis. 2009 Ingår i: Nutrition, metabolism, and cardiovascular diseases : NMCD. - : Elsevier BV. - 1590-3729 .- 0939-4753. ; 19:5, s. 327-333 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND AIMS: Impaired glucose tolerance (IGT) is regarded as a transient metabolic state leading to type-2 diabetes, and is known to predict future risk of cardiovascular disease. This study was designed to investigate if IGT is associated with subclinical atherosclerosis. METHODS AND RESULTS: In a population-based cohort of 64-year-old women, a group with IGT determined by repeated oral glucose tolerance tests (n=205) was compared with healthy women with normal glucose tolerance (NGT, n=188). Intima-media thickness (IMT) and plaques in the common carotid arteries (CCA) and bulbs were measured by ultrasound. The 95% confidence interval (CI) of the difference between the IGT and NGT groups was -0.03 to 0.03mm. There was no difference in carotid bulb IMT or in the occurrence, size, and characteristics of plaques between the IGT and NGT groups. A meta-analysis was used to calculate summary measures of 12 reviewed studies showing a difference of 0.030 (95% CI 0.012-0.048) mm in carotid IMT between IGT and NGT groups. Heterogeneity in IMT differences between studies was shown. CONCLUSIONS: In our population-based cohort of 64-year-old women, IGT was not associated with increased occurrence of subclinical atherosclerosis. However, a meta-analysis of 12 studies, including our current study, showed that IGT was associated with a small increase in the CCA IMT.
15.	Davidsson, Lisa, et al. (författare) Ultrasound-assessed plaque occurrence in the carotid and femoral arteries are independent predictors of cardiovascular events in middle-aged men during 10 years of follow-up. 2009 Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To examine if plaques in the carotid and femoral arteries were associated with cardiovascular events during a 10-year follow-up independently of usual risk factors for such diseases. METHODS: Plaque occurrence in both carotid arteries, and in the right femoral artery were assessed at baseline by B-mode ultrasound in a population-based sample of 58-year-old men (n=391) with no cardiovascular disease, and varying degrees of obesity and insulin sensitivity at entry. Anthropometry and blood pressure were recorded. Fasting venous blood samples were used for measurement of cardiovascular risk factors. Cardiovascular events occurring during follow-up were obtained by access to register data. RESULTS: Systolic blood pressure, serum triglycerides and waist-hip ratio as well as baseline occurrence of carotid and femoral plaques were associated with events. Logistic multi-variate analyses showed that carotid plaques (OR 2.09, 95% CI 1.05-4.16, p=0.037), femoral plaques (OR 1.99, 95% CI 1.01-3.91, p=0.047) and concomitant presence of carotid, and femoral plaques (OR 2.53, 95% CI 1.23-5.21, p=0.011) were associated with cardiovascular events independently of other risk factors. Plaques occurred in 0-3 arteries and there was a parallel increase in cardiovascular risk (p=0.004). CONCLUSION: Occurrence of carotid or femoral plaques at baseline had similar predictive value for cardiovascular events. Increased plaque burden, with plaques in both carotid and femoral arteries increased the cardiovascular risk further. Hence, the results from this study indicate that ultrasound examination of both the carotid and femoral arteries was the preferred method to predict cardiovascular risk.
16.	Drivelegka, Panagiota, et al. (författare) Association between serum level of urate and subclinical atherosclerosis: results from the SCAPIS Pilot 2020 Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22 Tidskriftsartikel (refereegranskat)abstract Background Hyperuricemia is closely associated with cardiovascular disease (CVD). However, it has not been definitively established whether this association is independent of traditional cardiovascular risk factors (CVRFs) and whether it is gender-dependent. The aim of this study was to investigate in a population-based cohort (age range, 50-64 years) stratified by sex the association between the serum urate (SU) concentration and subclinical atherosclerosis, as reflected in the coronary artery calcification (CAC) score, common carotid intima-media thickness (CIMT), and carotid plaque score. Methods The study involved participants in the Swedish CArdioPulmonary bioImage Study (SCAPIS) Pilot cohort (N = 1040; 48.8% males). This pilot cohort is part of the large population-based SCAPIS with 30,000 participants in the age range of 50-64 years, aimed at improving risk prediction for CVD. Subjects with a self-reported previous history of CVD (N = 68) or gout (N = 3) were excluded. The CAC score was assessed with the Agatston method using computed tomography. CIMT and carotid plaques were quantified by ultrasound. The associations between the SU quartiles and different levels of CAC, CIMT, and carotid plaques were assessed by multivariable logistic regression. Results Age, BMI, education level, smoking, physical activity, hs-CRP, hypertension, and dyslipidemia showed no differences between males and females, while CAC (score > 0) and diabetes were both twice as common in men than in women (58% vs 26% and 8% vs 4%, respectively). Higher SU quartiles were in both sexes associated with BMI, hs-CRP, and the prevalence of hypertension, and in women, they were also associated with the prevalence of dyslipidemia. The three upper quartiles of SU (>308 mu mol/L) were linked to higher CAC scores in men, when adjusting for CVRFs, but not in women. CIMT and carotid plaques showed no correlation to SU in either sex. Conclusions Higher levels of SU are associated with the presence of CAC in men but not in women, whereas SU is not associated with CIMT or carotid plaques in either men or women. This implies that the biological effects of SU differ in men and women or that SU has varying effects on different vascular beds or during the different stages of the atherosclerotic process.
17.	Ekblom Bak, Elin, 1981-, et al. (författare) Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study 2022 Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880 Tidskriftsartikel (refereegranskat)abstract The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
18.	Ekblom-Bak, Elin, et al. (författare) Fitness attenuates the prevalence of increased coronary artery calcium in individuals with metabolic syndrome. 2018 Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 25:3, s. 309-316 Tidskriftsartikel (refereegranskat)abstract Background The association between cardiorespiratory fitness, physical activity and coronary artery calcium (CAC) is unclear, and whether higher levels of fitness attenuate CAC prevalence in subjects with metabolic syndrome is not fully elucidated. The present study aims to: a) investigate the independent association of fitness on the prevalence of CAC, after adjustment for moderate-to-vigorous physical activity and sedentary time, and b) study the possible attenuation of increased CAC by higher fitness, in participants with metabolic syndrome. Design Cross-sectional. Methods In total 678 participants (52% women), 50-65 years old, from the SCAPIS pilot study were included. Fitness (VO2max) was estimated by submaximal cycle ergometer test and moderate-to-vigorous physical activity and sedentary time were assessed using hip-worn accelerometers. CAC score (CACS) was quantified using the Agatston score. Results The odds of having a significant CACS (≥100) was half in participants with moderate/high fitness compared with their low fitness counterparts. Further consideration of moderate-to-vigorous physical activity, sedentary time and number of components of the metabolic syndrome did only slightly alter the effect size. Those with metabolic syndrome had 47% higher odds for significant CAC compared with those without metabolic syndrome. However, moderate/high fitness seems to partially attenuate this risk, as further joint analysis indicated an increased odds for having significant CAC only in the unfit metabolic syndrome participants. Conclusions Being fit is associated with a reduced risk of having significant CAC in individuals with metabolic syndrome. While still very much underutilized, fitness should be taken into consideration in everyday clinical risk prediction in addition to the traditional risk factors of the metabolic syndrome.
19.	Englund-Ögge, Linda, et al. (författare) Alcohol consumption in relation to metabolic regulation, inflammation, and adiponectin in 64-year-old Caucasian women: a population-based study with a focus on impaired glucose regulation 2006 Ingår i: Diabetes Care. - 0149-5992. ; 29:4, s. 908-13 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The aims of this study were to examine alcohol drinking patterns in women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) and to investigate whether alcohol intake was associated with improved insulin sensitivity, decreased biomarkers of inflammation, and increased adiponectin levels and if these effects were limited to dysmetabolic women. RESEARCH DESIGN AND METHODS: From a cohort of 64-year-old Caucasian women, 209 with type 2 diabetes, 205 with IGT, and 186 with NGT were recruited. Alcohol consumption and medication use were assessed by questionnaires. Anthropometric data were collected, and blood glucose, insulin, HDL cholesterol, triglycerides, C-reactive protein, white blood cell count, and serum adiponectin were measured. RESULTS: Compared with the NGT group, alcohol consumption was lower in the IGT group and lowest in the diabetes group. Mean alcohol intakes of >9.2 and > or =3-9 g/day were positively associated with adiponectin and insulin sensitivity (homeostasis model assessment [HOMA]), respectively, independently of obesity, metabolic control, and other confounders. Alcohol intake correlated negatively with inflammatory markers, although this did not remain after adjustment for HOMA and waist circumference. The inverse associations between alcohol consumption and factors related to the metabolic syndrome such as HOMA, waist circumference, and inflammatory markers were more obvious among women with diabetes and IGT than in healthy women. CONCLUSIONS: In these women, moderate alcohol consumption showed beneficial associations with the prevalence of type 2 diabetes, IGT, insulin sensitivity, and serum adiponectin. There is a need to clarify whether adiponectin may be a mechanistic link and also to clarify the clinical implications of these observations.
20.	Gummesson, Anders, 1973, et al. (författare) Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes 2021 Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 63 Tidskriftsartikel (refereegranskat)abstract Background: Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods: To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings: Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation: The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding: This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).
21.	Gummesson, Anders, 1973, et al. (författare) Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects 2018 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8 Tidskriftsartikel (refereegranskat)abstract Objectives This study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors. The study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50-64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation <= 40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models. NAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07-2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0-1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13-16.6). NAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.
22.	Hansson, Caroline, 1981, et al. (författare) Influence of ghrelin on the central serotonergic signaling system in mice 2014 Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 79, s. 498-505 Tidskriftsartikel (refereegranskat)abstract The central ghrelin signaling system engages key pathways of importance for feeding control, recently shown to include those engaged in anxiety-like behavior in rodents. Here we sought to determine whether ghrelin impacts on the central serotonin system, which has an important role in anxiety. We focused on two brain areas, the amygdala (of importance for the mediation of fear and anxiety) and the dorsal raphe (i.e. the site of origin of major afferent serotonin pathways, including those that project to the amygdala). In these brain areas, we measured serotonergic turnover (using HPLC) and the mRNA expression of a number of serotonin-related genes (using real-time PCR). We found that acute central administration of ghrelin to mice increased the serotonergic turnover in the amygdala. It also increased the mRNA expression of a number of serotonin receptors, both in the amygdala and in the dorsal raphe. Studies in ghrelin receptor (GHS-R1A) knock-out mice showed a decreased mRNA expression of serotonergic receptors in both the amygdala and the dorsal raphe, relative to their wild-type littermates. We conclude that the central serotonin system is a target for ghrelin, providing a candidate neurochemical substrate of importance for ghrelin's effects on mood. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
23.	Herlitz, Hans, 1946, et al. (författare) Albuminuria within the normal range and ultrasound assessed atherosclerosis in the AIR study – a 9-year follow-up of 58-year old clinically healthy men : Normoalbuminuria and intima media thickness 2009 Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 69:4, s. 512-517 Tidskriftsartikel (refereegranskat)abstract Background:Microalbuminuria, traditionally defined as 30–300 mg urinary albumin/24 h, predicts renal impairment and cardiovascular disease. Studies suggest that also a far lower urinary albumin excretion (UAE) can predict clinical outcome. Intima media thickness (IMT) is an established estimate of atherosclerosis. In this study, we investigated the predictive value of UAE within the normal rate (UAE–n) for the progression of IMT in the carotid and femoral arteries. Methods: We included 325 clinically healthy men with normoalbuminuria. Anthropometrics, urine and blood samples were taken and IMT in the carotid and femoral arteries were assessed by B–mode ultrasound at baseline and after 3 and 9 years. The annual progression rate of IMT (r–IMT) was calculated. Results: UAE–n correlated with carotid IMT at baseline and after 3 and 9 years, but not with r–IMT. In a regression analysis, only HDL and baseline IMT remained as statistically significant co–variates to mean IMT at 9 years. IMT in the femoral artery and r–IMT at any time–point did not correlate to baseline UAE. Conclusion: UAE–n was associated with carotid IMT after 3 and 9 years but not r–IMT or with femoral artery IMT. Carotid IMT after 9 years' follow–up was independently related to baseline IMT and HDL cholesterol. In this cohort of 58–year–old men, our interpretation is that UAE–n is not associated with the increase in carotid and femoral artery IMT observed after 9 years
24.	Hjelmgren, Ola, et al. (författare) A study of plaque vascularization and inflammation using quantitative contrast-enhanced US and PET/CT 2014 Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 83:7, s. 1184-1189 Tidskriftsartikel (refereegranskat)abstract Background: Contrast-enhanced ultrasound (CEUS) is an in vivo methodology to quantify carotid plaque vascularization. Increased metabolism in plaques, measured as FDG uptake in PET/CT examination, has been associated with markers of inflammation in histological samples. In this study, we tested the association between FDG uptake and vascularization measured by CEUS to assess whether CEUS can be used as an in vivo marker of plaque vulnerability. Methods: After informed consent, subjects aged >60 years with carotid plaque height exceeding 2.5 mm were recruited. CEUS was performed and analyzed using earlier described protocol and software, Contrast Quantification Program, which calculates the fraction of the plaque being contrast positive (CQP value). PET/CT examination was performed within 3 months of CEUS (median time 7 days). PET/CT images were acquired 90 min after FDG injection (2.7 MBq/kg). FDG uptake was measured as tissue background index (TBI), calculated using Spearman's rho as mean standard uptake value (SUV) of the plaque divided by mean Shy in the jugular vein (mean of 7 measuring points). Local ethics committee approved the study. Results: We recruited 13 subjects (5 women) with a mean age of 71 years, 6 had a history of stroke or TIA, 1 had a history of ipsilateral stroke. CQP values showed a significant, positive correlation with TBI of carotid plaques, r= 0.67, p <0.02. Conclusions: Plaque vascularization measured by CEUS correlates positively with FDG uptake measured by PET/CT in humans. This indicates an association between vascularization and inflammation and/or hypoxia, supporting the use of CEUS as a non-invasive method to detect plaque vulnerability. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
25.	Hjelmgren, Ola, et al. (författare) Beta-Cell Function, Self-rated Health, and Lifestyle Habits in 64-Year-Old Swedish Women with Metabolically Healthy Obesity Phenotype 2020 Ingår i: Journal of Obesity & Metabolic Syndrome. - : Korean Society for the Study of Obesity. - 2508-6235 .- 2508-7576. ; 29:1, s. 39-46 Tidskriftsartikel (refereegranskat)abstract Background: A subset of obese individuals do not present metabolic abnormalities that commonly define the metabolic syndrome (MetS). This is referred to as a metabolically healthy obese (MHO) phenotype. The aim of the present study was to evaluate the prevalence of the MHO phenotype and its relationship with beta cell dysfunction by measuring C-peptide and proinsulin, anthropometric-, metabolic- and lipid appearance, as well as lifestyle behaviors and self-rated health in a cohort of 64-year-old Swedish women. Methods: The National Cholesterol Education Program definition was used to assess MetS. We defined normal weight as body mass index (BMI) 18.5-24.9 kg/m(2) and obesity as BMI >= 30 kg/m(2) to categorize participants as metabolically healthy normal weight, MHO, and metabolically unhealthy obese. Results: The MHO phenotype represented 36.3% of obese participants and 16.3% of total participants. The MHO group were at greater risk of having proinsulin levels >11 pmol/L, indicating impaired beta cell function. Further, homeostatic model assessment for insulin resistance, fasting plasma levels of insulin, and C-peptide showed significant trends, with the MHO phenotype group having intermediate levels among three groups. Health behaviors such as leisure time physical activity and alcohol intake were also intermediate in individuals with the MHO phenotype. Conclusion: In this study, we demonstrate that over a third of the obese women in our sample were MHO. Further, women with the MHO phenotype showed intermediate profiles considering beta cell function and insulin resistance, as well as metabolic variables, and tended to rate their general health as worse than otherwise similar individuals of normal weight.
26.	Hjelmgren, Ola, et al. (författare) Comparison between magnetic resonance imaging and B-mode ultrasound in detecting and estimating the extent of human carotid atherosclerosis 2018 Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 38:2, s. 296-303 Tidskriftsartikel (refereegranskat)abstract Background In MRI studies of carotid plaques, ultrasound is used to find plaques, which are later imaged using MRI. The performance in plaque detection has not been compared between the modalities. The aim of the current study was to compare the performance of MRI and ultrasound in detecting carotid artery plaques and measuring extent of atherosclerosis. Methods Subjects with at least one plaque (height >= 2.5mm) on ultrasound were imaged using MRI. The number of plaques and their height was measured in both modalities; plaque area and volume were analysed on ultrasound and MRI, respectively. Results Thirty-eight subjects were included. MRI detected plaques in 95% of carotid arteries with a plaque height of 2.5 mm on ultrasound and in all carotid arteries with a plaque exceeding >= 2.5 mm. MRI detected 53% of the plaques with a height below 2.5mm. The plaque height measured with both techniques correlated significantly, 0.59, P<0.0001. Ultrasound-derived plaque height and plaque area correlated similarly to MRI-derived plaque volume, r = 0.52; P<0.0001 and r = 0.47; P = 0.001, respectively. Conclusions We conclude that MRI has a similar sensitivity to ultrasound in finding carotid artery plaques that are 2.5 mm or higher. In smaller plaques, MRI detects fewer plaques. Multiple carotid plaques seen on ultrasound most often are a misinterpretation of the anatomy and correspond to a single plaque. Plaque height on ultrasound is comparable to plaque height on MRI and correlates fairly well with plaque volume on MRI making it an interesting proxy for plaque burden.
27.	Hjelmgren, Ola, et al. (författare) Identification of Vascularised Carotid Plaques Using a Standardised and Reproducible Technique to Measure Ultrasound Contrast Uptake 2013 Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 46:1, s. 21-28 Tidskriftsartikel (refereegranskat)abstract Objectives: Contrast-enhanced ultrasonography (CEUS) has been used to assess the vascularisation of carotid plaques. Our aim was to develop and validate a standardised semi-automated method for CEUS examination of plaques, and test if the technique could be used to identify vulnerable plaques. Methods: Study participants were a mixed population of symptomatic and asymptomatic subjects, selected if they had a plaque with height >2.5 mm and <10% acoustic shadowing. Participants received a bolus of ultrasound contrast agent and a 90-s cine-loop was captured. A Contrast Quantification Program (CQP) was developed and trained to identify extent of contrast uptake after motion correction and application of a noise reduction algorithm. The technique was validated by comparing CQP values with visual assessment of contrast uptake. CQP values were also compared with plaque echogenicity and history of clinical events. Results: CQP values correlated with a visual, 5-scale classification of contrast uptake by two blinded, experienced sonographers. Repeated contrast injections showed high reproducibility. Participants with a history of ipsilateral stroke/TIA had significantly higher CQP values than asymptomatic participants. Conclusion: We present a reproducible, semi-automatic method to identify vascularisation of carotid plaques, which could be used in prospective studies to determine the clinical value of plaque vascularisation. (C) 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
28.	Hjelmgren, Ola, et al. (författare) Inverse association between size of the lipid-rich necrotic core and vascularization in human carotid plaques 2018 Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 38:2, s. 326-331 Tidskriftsartikel (refereegranskat)abstract Purpose To study the relationship between the size of the lipid-rich necrotic core measured by MRI (magnetic resonance imaging) and the level of plaque vascularization measured by contrast-enhanced ultrasound, in human carotid plaques. Further, to compare the size of lipid-rich necrotic core from MRI to plaque echogenicity. Methods Thirty-one subjects with carotid plaques underwent standard B-mode ultrasound, contrast-enhanced ultrasound and MRI. The lipid-rich necrotic core was quantified using MRI. Contrast-enhanced ultrasound was used to measure carotid plaque vascularization. Standard B-mode ultrasound was used to measure plaque echogenicity as greyscale median. Results The amount of lipid-rich necrotic core correlated inversely with the degree of plaque vascularization (r = -0.40, P = 0.03). There were no correlations between the degree of plaque vascularization and the amount of fibrous tissue or calcifications. There were no correlations between greyscale median and the lipid-rich necrotic core, fibrous tissue or calcifications. Conclusions We show that more dense plaque vascularization is associated with a lower plaque content of lipid-rich necrotic core. A large lipid-rich necrotic core and high plaque vascularization are both proposed as predictors of vulnerability, and our finding is therefore odds with some earlier observations. Our finding can be explained by the fact that the necrotic core of the plaque contains no viable tissue and therefore less of the plaque can be vascularized if the lipid-rich necrotic core is large. Our study suggests that the true relation between plaque vascularization and other indices of vulnerability is more complex than initially thought.
29.	Hägg, Daniel, 1974, et al. (författare) Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages. 2006 Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 185:2, s. 282-9 Tidskriftsartikel (refereegranskat)abstract Using DNA microarray analysis, we found that human macrophages respond to oxidized low-density lipoprotein (oxLDL) by activating the antioxidative glutathione and thioredoxin systems. Several genes of the glutathione and thioredoxin systems were expressed at high levels in macrophages when compared to 80 other human tissues and cell types, indicating that these systems may be of particular importance in macrophages. The up-regulation of three genes in these systems, thioredoxin (P < 0.005), thioredoxin reductase 1 (P < 0.001) and glutathione reductase (P < 0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors. To investigate the possible role of these antioxidative systems in the development of atherosclerosis, expression levels in macrophages from 15 subjects with atherosclerosis (12 men, 3 women) and 15 matched controls (12 men, 3 women) were analyzed using DNA microarrays. Two genes in the glutathione system Mn superoxide dismutase (P < 0.05) and catalase (P < 0.05) differed in expression between the groups. We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.
30.	Johansson, Karin, et al. (författare) Ankle-Brachial Index Should Be Measured in Both the Posterior and the Anterior Tibial Arteries in Studies of Peripheral Arterial Disease 2010 Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 61:8, s. 780-783 Tidskriftsartikel (refereegranskat)abstract Lower extremity peripheral artery disease (PAD) is a powerful predictor of cardiovascular events and mortality. The ankle-brachial index (ABI) is an objective and standard diagnostic method to diagnose PAD (an ABI ≤0.9 is considered pathological). The American Heart Association (AHA) and the American College of Cardiology (ACC) recommend using both the posterior- and anterior tibial arteries when assessing ABI. We investigated if there was a difference in the diagnosis of PAD if the ABI was measured in the posterior- or the anterior tibial artery. The results showed that among subjects with ABI ≤0.9, between 30% and 40% would not get a PAD diagnosis if the ABI was measured in only 1 of the arteries. In conclusion, this study emphasizes the importance of measuring the ABI in both the posterior tibial and the anterior tibial arteries when diagnosing PAD.
31.	Johansson, Lisa, et al. (författare) Increased apoB/apoA-I ratio is predictive of peripheral arterial disease in initially healthy 58-year-old men during 8.9 years of follow-up 2009 Ingår i: Angiology. ; 60:5, s. 539-545 Tidskriftsartikel (refereegranskat)abstract The aim of the present study was to investigate, if increased levels of apoB/apoA-I ratios are associated with future peripheral arterial disease as measured by ankle-brachial index. Increased apoB/apoA-I levels are defined as 0.9, which has been suggested for men, and as 0.63, which has observed to be associated with plaques in the femoral artery. The study was performed in a cohort of initially clinically healthy 58-year-old men living in the city of Göteborg, Sweden.The group with an apoB/apoA-I ratio > or =0.9 had a significantly increased risk of having PAD during 8.9 years of follow-up than the group below that level (OR: 2.15 CI: 1.21 to 3.82, p < 0.01). When applying the lower apoB/apoA-I cut off, results showed that the group with a level >0.63 had more than a three-fold risk of future PAD compared to the group < or =0.63 (OR: 3.28 CI: 1.14 to 9.40, p < 0.05).
32.	Kalman, Janos L, et al. (författare) Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study. 2019 Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75 Tidskriftsartikel (refereegranskat)abstract Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
33.	Karlsson-Lindahl, Linda, 1972, et al. (författare) Heparanase affects food intake and regulates energy balance in mice. 2012 Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:3 Tidskriftsartikel (refereegranskat)abstract Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.
34.	Koh, Ara, et al. (författare) Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1 2018 Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 175:4 Tidskriftsartikel (refereegranskat)abstract Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38 gamma MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.
35.	Liao, X., et al. (författare) Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin? 2016 Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:11, s. 1165-1173 Tidskriftsartikel (refereegranskat)abstract Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions. © 2016 European Society of Cardiology.
36.	Lorenz, M. W., et al. (författare) Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration 2015 Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:10, s. 1921-1929 Tidskriftsartikel (refereegranskat)abstract OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
37.	Lorenz, Matthias W., et al. (författare) Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project) : a meta-analysis of individual participant data 2012 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 379:9831, s. 2053-2062 Tidskriftsartikel (refereegranskat)abstract Background Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association. Methods: We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis. Findings: Of 21 eligible studies, 16 with 36 984 participants were included. During a mean follow-up of 7.0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2-7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0.97 (95% CI 0.94-1.00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0.98 (0.95-1.01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1.16, 95% CI 1.10-1.22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=-0.06 and r=-0.02). Interpretation: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials.
38.	Lorenz, M. W., et al. (författare) Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration 2018 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4 Tidskriftsartikel (refereegranskat)abstract Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
39.	Malmgren Fänge, Agneta, et al. (författare) The TECH@HOME study, a technological intervention to reduce caregiver burden for informal caregivers of people with dementia: study protocol for a randomized controlled trial 2017 Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:63 Tidskriftsartikel (refereegranskat)abstract Background: It is estimated that global dementia rates will more than triple by 2050 and result in a staggering economic burden on families and societies. Dementia carries significant physical, psychological and social challenges for individuals and caregivers. Informal caregiving is common and increasing as more people with dementia are being cared for at home instead of in nursing homes. Caregiver burden is associated with lower perceived health, lower social coherence, and increased risk of morbidity and mortality. The aim of this trial is to evaluate the effects of information and communication technology (ICT) on caregiver burden among informal caregivers of people with dementia by reducing the need for supervision. Methods/design: This randomized controlled trial aims to recruit 320 dyads composed of people with dementia living in community settings and their primary informal caregivers. In the intervention group, people with dementia will have a home monitoring kit installed in their home while dyads in the control group will receive usual care. The ICT kit includes home-leaving sensors, smoke and water leak sensors, bed sensors, and automatic lights that monitor the individual's behavior. Alerts (text message and/or phone call) will be sent to the caregiver if anything unusual occurs. All study dyads will receive three home visits by project administrators who have received project-specific training in order to harmonize data collection. Home visits will take place at enrollment and 3 and 12 months following installation of the ICT kit. At every home visit, a standardized questionnaire will be administered to all dyads to assess their health, quality of life and resource utilization. The primary outcome of this trial is the amount of informal care support provided by primary informal caregivers to people with dementia. Discussion: This is the first randomized controlled trial exploring the implementation of ICT for people with dementia in a large sample in Sweden and one of the first at the international level. Results hold the potential to inform regional and national policy-makers in Sweden and beyond about the cost-effectiveness of ICT and its impact on caregiver burden.
40.	Månsson, Marianne, 1964, et al. (författare) Lp(a) is not associated with diabetes but affects fibrinolysis and clot structure ex vivo 2014 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4 Tidskriftsartikel (refereegranskat)abstract Lipoprotein (a) [Lp(a)] is a low density lipoprotein (LDL) with one apolipoprotein (a) molecule bound to the apolipoprotein B-100 of LDL. Lp(a) is an independent risk factor for cardiovascular disease (CVD). However, the relationship of Lp(a) to diabetes and metabolic syndrome, both known for increased CVD risk, is controversial. In a population based study on type two diabetes mellitus (T2DM) development in women, Lp(a) plasma levels showed the well known skewed distribution without any relation to diabetes or impaired glucose tolerance. A modified clot lysis assay on a subset of 274 subjects showed significantly increased clot lysis times in T2DM subjects, despite inhibition of PAI-1 and TAFI. Lp(a) plasma levels significantly increased the maximal peak height of the clot lysis curve, indicating a change in clot structure. In this study Lp(a) is not related to the development of T2DM but may affect clot structure ex vivo without a prolongation of the clot lysis time.
41.	Olson, Fredrik J., 1975, et al. (författare) Circulating matrix metalloproteinase 9 levels in relation to sampling methods, femoral and carotid atherosclerosis. 2008 Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 263:6, s. 626-35 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To examine whether circulating levels of matrix metalloproteinase 9 (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and echolucent plaques in the carotid and femoral arteries. To examine preanalytical sources of variability in MMP-9 concentrations related to sampling procedures. SUBJECTS AND DESIGN: Plasma and serum MMP-9 levels were compared with ultrasound assessed measures of femoral and carotid atherosclerosis, in a cross-sectional study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9 levels were examined in 10 healthy subjects. Main outcome measures were circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral arteries, and plaque status based on size and echolucency. SETTING: Research unit at university hospital. RESULTS: Plasma concentrations of total and active MMP-9 were associated with femoral artery IMT independently of traditional cardiovascular risk factors, and were higher in subjects with moderate to large femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent femoral plaques (P = 0.006) compared with subjects without femoral plaques. No similar associations were found for carotid plaques. MMP-9 concentrations were higher in serum than in plasma, and higher when sampling was performed with Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated with peripheral neutrophil count compared with MMP-9 levels in plasma. CONCLUSIONS: Plasma MMP-9 levels were associated with atherosclerosis in the femoral artery, and total MMP-9 concentration was higher in men with echolucent femoral plaques. The choice of sample material and sampling method affect the measurements of circulating MMP-9 levels.
42.	Ryndel, Mikael, 1982, et al. (författare) The haptoglobin 2-2 genotype is associated with carotid atherosclerosis in 64-year old women with established diabetes. 2010 Ingår i: Clinica chimica acta; international journal of clinical chemistry. - : Elsevier BV. - 1873-3492. Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Haptoglobin polymorphism generates three common human genotypes: Hp1-1, Hp2-1 and Hp2-2. Among subjects with diabetes, Hp2-2 is associated with an elevated risk to develop cardiovascular disease. The impact of haptoglobin genotype on subclinical carotid atherosclerosis is not known. We hypothesised that Hp2-2 was associated with increased occurrence of carotid atherosclerosis in subjects with diabetes. METHODS: We studied a population-based sample of 64-year old women with diabetes (n=226), either established diabetes known before study entry (n=116) or new diabetes detected at study screening. Haptoglobin genotype was determined by PCR. Carotid atherosclerosis was assessed by ultrasound imaging. RESULTS: In the entire diabetes cohort, no differences were observed in carotid intima-media thickness (IMT) or plaque prevalence between the genotype groups. However, among those with established diabetes, Hp2-2 was associated with higher plaque prevalence and larger carotid IMT compared with the Hp2-1 and Hp1-1 genotypes. Common cardiovascular risk factors did not differ between the genotype groups. CONCLUSIONS: The Hp2-2 genotype was associated with increased occurrence of subclinical carotid atherosclerosis in 64-year old women with established diabetes. This association was not explained by traditional risk factors for cardiovascular disease. These results extend previous observations that Hp2-2 is associated with clinical cardiovascular disease in diabetes.
43.	Schmidt, Caroline, 1966, et al. (författare) 58-year old men witn non-stenotic carotid artery plaques, and the relationship with cardiovascular risk factors and future cardiovascular events 2005 Ingår i: Vascular disease prevention. ; 2, s. 129-134 Tidskriftsartikel (refereegranskat)abstract Objectives. The main aim of the present study was to examine the relationship between plaque occurrence and size, assessed by B-mode ultrasound in the carotid arteries, cardiovascular risk factors and the development of clinical cardiovascular disease. A further exploratory aim was to assess the relationship between plaque echogenicity and the development of cardiovascular disease. Methods. The carotid arteries were examined bilaterally by high-resolution B-mode ultrasound in 391, 58-year old men, identified by screening in the city of Göteborg, Sweden. Assessment of plaque occurrence, plaque size (No, Small, Moderate/Large) and plaque characteristics in terms of echogenicity (No, Echogenic or Echolucent) were performed. Results. Systolic blood pressure was significantly associated with plaque occurrence at baseline (OR 2.31, 95% CI 1.51 to 3.55). Total cholesterol and systolic blood pressure were significantly associated with cardiovascular events during follow-up (total cholesterol,=1.2011, SE=0.5243, p-value=0.0220, systolic blood pressure, =1.5171, SE=0.5658, p-value=0.0073, respectively). The odds ratio for suffering cardiovascular events among subjects with plaques were 1.64 (95% CI 0.63 to 4.26). Conclusions. Systolic blood pressure was a significant predictor for plaque occurrence at baseline. Total cholesterol and systolic blood pressure, but not plaque occurrence were both significant predictors of cardiovascular events during follow-up. The study had limited power to detect the impact of plaque echogenicity on risk.
44.	Schmidt, Caroline, 1966, et al. (författare) apoB/apoA-I ratio is related to femoral artery plaques and is predictive for future cardiovascular events in healthy men 2006 Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 189:1, s. 178-85 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: The aim of the present study was to investigate the association between serum concentrations of apoB, apoA-I and the apoB/apoA-I ratio and future cardiovascular events in a group of healthy 58-year-old men during 6.6 years of follow-up. A further aim was to investigate the concentrations of apoB, apoA-I and the apoB/apoA-I ratio to the association of plaque occurrence in the carotid and femoral arteries. BACKGROUND: Previous studies have shown that the apoB/apoA-I ratio is an important cardiovascular risk factor, whereas the association between apoB/apoA-I ratio and presence of atherosclerotic plaques in the carotid and femoral arteries has been less investigated. METHODS: The carotid and femoral arteries were examined by high-resolution B-mode ultrasound in 391, 58-year-old men identified by screening in the city of Goteborg, Sweden. Assessment of plaque occurrence and measurement of apolipoproteins (apoA-I and apoB) was performed. RESULTS: Subjects with an apoB/apoA-I ratio >/=0.9 had a significantly increased risk to suffer a cardiovascular event during 6.6 years of follow-up (OR 3.07, 95% CI 1.22-7.71), while no difference in risk for cardiovascular events was observed for subjects with LDL cholesterol >3.4 mmol/L compared to subjects <3.4 mmol/L (OR 1.04, 95% CI 0.37-2.46). A greater risk for plaques in the femoral artery was also observed in subjects with an apoB/apoA-I ratio >/=0.9 compared to subjects <0.9 (OR 3.06, 95% CI 1.22-7.70). In a multiple logistic regression model, both elevated apoB/apoA-I ratio and plaque occurrence in the femoral artery were of significant importance for cardiovascular events during follow-up. CONCLUSIONS: The results showed that the apoB/apoA-I ratio was associated with arteriosclerosis in the femoral artery, and predicted future cardiovascular events. These observations, and the fact that apoB and apoA-I can be measured in the non-fasting state with high precision, in combination with the finding that LDL cholesterol did not predict cardiovascular disease, support results from other studies that the apoB/apoA-I ratio may be a superior risk marker for cardiovascular disease.
45.	Schmidt, Caroline, 1966, et al. (författare) ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol 2008 Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 196:2, s. 817-822 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: The apolipoproteinB (apoB)/apolipoproteinA-I (apoA-I) ratio mirrors the number of pro-atherogenic and anti-atherogenic lipoprotein particles. This ratio may carry more information on risk for atherosclerosis than LDL in cohorts with impaired glucose tolerance. The aim was to examine the association between the apoB/apoA-I ratio and ultrasound-assessed atherosclerosis in the carotid and femoral arteries in women with varying degrees of glucose tolerance. METHODS: Plaque occurrence, and intima-media thickness in the carotid and femoral arteries were examined by B-mode ultrasound in a random sample of 64-year-old women (n=646) living in Gothenburg, Sweden, representing different degrees of glucose intolerance (diabetes (n=234), impaired (n=212) and normal glucose tolerance (n=200)). Traditional risk factors and serum concentrations of apolipoproteins were analysed. RESULTS: For subjects in the lowest LDL tertile, the risk of having a plaque in the femoral artery was three times greater for subjects in the highest apoB/apoA-I tertile compared to subjects in the lowest tertile (OR: 3.0, 95% CI: 1.2-7.5). A clear increase in the occurrence of femoral plaque was observed already at a cut-off value of 0.63 (OR: 1.8, 95% CI: 1.2-2.6). ApoB/apoA-I was also related to femoral plaque occurrence in women with low HbA1c. ApoB/A-I ratio was associated with carotid and femoral IMT but not carotid plaques. CONCLUSION: The apoB/apoA-I ratio improved the identification of cases with femoral artery atherosclerosis in a cohort of women with varying degrees of glucose tolerance. Such cases could also be identified in women with normal LDL and HbA1c levels. The results indicate that an apoB/apoA-I ratio above 0.63 should be used as a marker of increased risk.
46.	Schmidt, Caroline, 1966, et al. (författare) Apolipoprotein B and Apolipopotein A-I in Vascular Risk Prediction - A Review 2014 Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1381-6128. ; 20:40, s. 6289-6298 Tidskriftsartikel (refereegranskat)abstract The concentration of low-density lipoprotein cholesterol has long been generally accepted as one of the strongest, independent risk factors for the development of cardiovascular disease. However, an increasing number of studies suggest that the ratio of apolipoprotein B (apoB) to apolipoprotein A-I (apoA-I) is a better risk predictor. In the present review, we focus on apoB and apoA-I as factors in predicting vascular risk in epidemiological studies only, and not in studies involving pharmaceutical intervention. The majority of studies in the present review show that apoB and the apoB/apoA-I ratio are independently and more strongly associated with vascular risk across varying age-groups and geographic regions than are conventional lipids, lipoproteins and lipid ratios.
47.	Schmidt, Caroline, 1966, et al. (författare) Apolipoprotein B/Apolipoprotein A-I Ratio and Apolipoprotein B: Long-Term Predictors of Myocardial Infarction in Initially Healthy Middle-Aged Men-a 13-Year Follow-Up 2014 Ingår i: International Journal of Offender Therapy and Comparative Criminology. - : SAGE Publications. - 0306-624X. ; 65:10, s. 901-905 Tidskriftsartikel (refereegranskat)abstract We investigated whether serum concentrations of apolipoprotein (apo) B and apoA-I and the apoB/apoA-I ratio provided predictive information on myocardial infarction (MI) and ischemic stroke during 13 years of follow-up in a group of initially clinically healthy 58-year-old men, free from previous cardiovascular disease, diabetes, other established disease, or treatment with cardiovascular drugs. Multivariate logistic regression analysis showed that the apoB/apoA-I ratio and apoB were significant and independent determinants of MI (exponentiation of the B coefficient [Exp()] 3.1, 95% confidence interval [CI] 1.6-6.3, P = .001, Exp() 2.8, 95% CI 1.1-7.7, P = .045, respectively). The area under the receiver-operating characteristics curve as a relative measure of test efficiency was highest and significant for both apoB/apoA-I ratio and apoB (area under the curve = 0.75, P < .001). In conclusion, the apoB/apoA-I ratio and apoB are independent risk factors for MI and has the highest efficiencies for predicting MI in initially healthy middle-aged men.
48.	Schmidt, Caroline, 1966, et al. (författare) Baseline ICAM-1 and VCAM-1 Are Increased in Initially Healthy Middle-Aged Men Who Develop Cardiovascular Disease During 6.6 Years of Follow-Up 2009 Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 60:1, s. 108-114 Tidskriftsartikel (refereegranskat)abstract The objective of the present study was to investigate if there was a difference in baseline serum concentrations of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) between groups with and without cardiovascular events during a mean follow-up of 6.6 years in a group of initially healthy 58-year-old men. A further aim was to examine if high serum concentrations of ICAM-1 and VCAM-1 were associated with carotid and femoral artery plaque occurrence, separately. Men with cardiovascular events during follow-up had higher median serum ICAM-I and VCAM-I than those without events (P < .05). The median of serum ICAM-I and VCAM-1 in the event group was used as the cutoff level, and in those with ICAM-1 and VCAM-1 above the cutoff value, there was an increased risk of having a plaque in the femoral artery (OR = 2.8, 95% CI = 1.8-4.3; and OR = 1.6, 95% CI = 1.1-2.5, respectively).
49.	Schmidt, Caroline, 1966, et al. (författare) Carotid Artery Intima-Media Thickness Predicts Major Cardiovascular Events During 7-Year Follow-Up in 64-Year-Old Women Irrespective of Other Glucometabolic Factors 2017 Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 68:6, s. 553-558 Tidskriftsartikel (refereegranskat)abstract Cardiovascular (CV) disease (CVD) is a leading cause of morbidity and mortality worldwide. Most CV events are caused by atherosclerosis. Diabetes and impaired glucose tolerance are associated with greater carotid intima-media thickness (IMT) and increased risk for CVD. The present study examined if common carotid artery IMT (CCAIMT) is predictive of CVD irrespective of glucose tolerance category and glycated hemoglobin (HbA1c) in a sample of 639 women with different glucose tolerance categories. During 7-year follow-up, 30 events in the cardiac and 32 events in the cerebral territory were documented. Unadjusted Cox hazard models showed that CCAIMT, glucose tolerance category, and HbA1c were associated with increased risk. An adjusted and extended model, including CCAIMT, glucose tolerance category, and HbA1c, showed that CCAIMT was still associated with events with an almost unchanged hazard ratio. In conclusion, this study suggests that CCAIMT is predictive of major CV events during 7-year follow-up, irrespective of glucose tolerance category, HbA1c, and other established risk factors in a cohort of 64-year-old women.
50.	Schmidt, Caroline, 1966, et al. (författare) Chlamydia pneumoniae seropositivity is associated with carotid artery intima-media thickness 2000 Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 31:7, s. 1526-1531 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND PURPOSE: Infection may both augment the atherosclerotic process and contribute to later manifestations of overt clinical disease. Chlamydia pneumoniae elementary bodies have been detected in atherosclerotic lesions. The aim of the present study was to investigate whether elevated titers of antibodies and circulating immune complexes to C pneumoniae were associated with ultrasound findings indicating presence of atherosclerosis in the carotid artery. METHODS: Serum titers of antibodies to C pneumoniae (IgM, IgA, IgG, and circulating immune complex) were related to intima-media thickness (IMT) and plaque status measured by B-mode ultrasound in the carotid artery in 113 men with treated hypertension and at least 1 of the following risk factors: hypercholesterolemia, smoking, or diabetes. RESULTS: Any of the titers was elevated in 56 (50%) men, and common carotid artery IMT was thicker in this group compared with the 57 men without any elevated titers (1.00 versus 0.92 mm, P<0.05). There were no accompanying differences in blood pressure, lipid levels, blood glucose, or smoking. Elevation of separate antibody types and circulation immune complex were also associated with increased IMT. In the latter group, systolic blood pressure was higher among seropositive patients compared with those who had no circulating immune complex. Seropositivity was not related to plaque status. CONCLUSIONS: Seropositivity for C pneumoniae was associated with an increased intima-media thickness in the common carotid artery but not plaque status in hypertensive men at high risk for cardiovascular disease.

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