| 1. |
- Djekic, Demir, 1989-
(författare)
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Novel and Traditional Risk Factors for Coronary Artery Disease : Role of Coronary Artery Calcium, Lipidomics, Psychosocial Factors and Diet
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The aim of the research reported in this thesis was to determine the association of novel and traditional risk factors with coronary artery calcium (CAC), a marker of subclinical coronary artery disease (CAD) in healthy individuals. In addition, we investigated the effects of a vegetarian, compared to a meat diet, on novel and traditional risk factors in patients with diagnosed CAD.Methods: Studies I-II evaluated the inter-laboratory reproducibility of liquid chromatography-mass spectrometry (LC-MS) lipid analysis and the association of serum lipidome with CAC in a cohort of 70 patients. Studies III and IV analysed data of 1067 participants in the pilot study of the Swedish CArdioPulmonary bioImage Study to determine associations of psychosocial (residential area, education, housing, and social support) and traditional risk factors with CAC. Cardiac computed tomography was used to obtain a coronary artery calcium score (CACS) (Studies I–IV). Study V employed a crossover design in which 31 patients with CAD were randomly allocated to a four-week vegetarian diet alternating with four weeks of an isocaloric meat diet. Enzyme-linked immunosorbent assay was used to measure oxidised LDL-cholesterol. Plasma metabolome, including choline, trimethylamine N-oxide, L-carnitine, and acetyl-carnitine, as well as plasma lipidome were determined with LC-MS. Gut microbiota and faecal short- and branched-chain fatty acids were analysed with 16S rRNA gene sequencing and gas chromatography-MS, respectively.Results: In Study I, two laboratories independently identified six lipids in common that differentiated serum of patients with CACS >250 from that of those with CACS=0. Study II, revealed higher levels of phosphatidylcholine(PC)(16:0/20:4) and lower levels of PC(18:2/18:2), PC(36:3) and phosphatidylethanolamine (PE)(20:0/18:2) in patients with CACS >250 than found in those with CACS=0. Study III showed a CACS >0 prevalence of 46.3% and 36.6% in low and high socioeconomic residential areas, respectively, but the traditional risk factor–adjusted odds ratio for CACS >0 was not significantly higher in subjects living in low socioeconomic areas. In Study III, the traditional risk factor–adjusted odds ratio for CACS >100 relative to CACS=0 was significantly higher in women with low education level and living in a rented apartment. Studies III and IV showed traditional risk factor–adjusted odds ratios for CACS >0 to be significantly higher in women with a family history of premature cardiovascular disease and low social support. No relationship of psychosocial factors with CAC was observed in men. The vegetarian diet implemented in Study V significantly lowered mean oxidized LDL-cholesterol (-2.73 U/L), total cholesterol (-0.13 mmol/L), LDL-cholesterol (-0.10 mmol/L), and body mass index (-0.21 kg/m2), as well as the relative abundance of PCs, PEs, and several microbial genera compared with the meat diet. The effect of the vegetarian diet on oxidized LDL-C was associated with higher relative abundance of Ruminococcaceae genera and of Barnesiella and reduced abundance of Flavonifractor. The vegetarian diet lowered the relative abundance of ceramide(d18:1/16:0) and triacylglycerols with saturated fatty acyl chains and raised the relative abundance of triacylglycerols with high carbon and polyunsaturated fatty acyl chains compared with the meat diet.Conclusions: Novel and traditional cardiovascular risk factors are associated with subclinical CAD. Psychosocial factors are associated with subclinical CAD in women, but not in men. Short-term intervention with a vegetarian diet in individuals with CAD can positively impact novel and traditional factors that have been associated with risk of future cardiovascular events.
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| 2. |
- Khalili, Payam, 1977-
(författare)
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Risk factors for cardiovascular events and incident hospital-treated diabetes in the population
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Well-established risk factors for CVD include increasing age, male sex, sedentary lifestyle, obesity, smoking, diabetes, hypertension, dyslipidaemia and low socio-economic status. Traditional risk factors do, however, not fully explain cardiovascular risk in general. In this thesis we focused on two conventional risk factors (smoking, blood pressure), and two unconventional risk markers (adiponectin, an adipocyte derived protein; and sialic acid (SA), a marker of systemic inflammation) for prediction of CVD events.Aims: In Paper I we examined to what degree smoking habits modify the risk of CVD in relation to systolic blood pressure levels in middle-aged men. In Paper II we investigated the predictive role of adiponectin for risk of CVD as well as the cross-sectional associations between adiponectin and markers of glucose metabolism, also in men. In Paper III we examined if increasing pulse pressure (PP) and increasing levels of SA both increase the risk of CVD and whether their effects act in synergism. In Paper IV the association of SA with risk of incident diabetes mellitus and related complications, resulting in hospitalization, was studied.Subjects and Methods: Two large-scale, population-based, screening studies with long follow-up periods have been used. The Malmö Preventive Project (MPP) was used with 22,444 individuals in Paper I and a sub cohort of 3,885 individuals in Paper II. The Värmland Health Survey (VHS) was used in Papers III and IV with 37,843 and 87,035 individuals, respectively.Results: CVD risk increases with increasing systolic blood pressure levels and this risk is almost doubled in smokers. Total adiponectin level is not associated with increased risk of future CVD but it is inversely associated with markers of glucose metabolism. PP and SA both contribute to risk of future CVD. Adjustment for mean arterial pressure reduces the risk induced by PP. Elevated SA contributes to increased risk of incident diabetes and related complications leading to hospitalization.
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| 3. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 4. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 5. |
- Garvin, Peter, 1976-
(författare)
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Plasma levels of matrix metalloproteinase‐9 in a normal population : a psychoneuroendocrinological approach
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several large‐scale epidemiological studies have demonstrated the prognostic significance of psychosocial factors and stress for coronary artery disease (CAD). Observations of sudden changes in CAD incidence have led to the proposal of mechanisms regarding atherosclerotic plaque vulnerability. The collagen‐degrading enzyme matrix metalloproteinase-9 (MMP-9) is increased in rupture‐prone plaques with high inflammatory activity, and circulating levels of MMP-9 are raised in patients with acute coronary syndrome. However, the distribution of MMP‐9 levels and its relations to psychosocial factors and the stress hormone cortisol have not been previously explored in a normal population.The aim of this dissertation was to examine in a normal population the association of circulating levels of MMP-9 with traditional cardiovascular risk factors including levels of C-reactive protein (CRP), with psychosocial factors, and with saliva levels of cortisol. In addition, the reliability of a new method of ambulatory saliva sampling for assessment of cortisol levels was evaluated. A sub‐sample of the Life conditions, Stress, and Health (LSH)-study, a population based study exploring psychoneuroendocrinological pathways mediating the differences in CAD incidence over socioeconomic status, was used. Plasma levels of MMP-9 were examined in a sample randomly drawn from the LSH‐study (n=400), aged 45 to 69 years at enrollment.The main findings were: 1) there was a positive association between plasma MMP-9 levels and total risk load of cardiovascular risk factors. The findings were persistent after adjusting for CRP and could not be attributed to a single risk factor. 2) After adjusting for traditional cardiovascular risk factors and CRP, MMP-9 levels were positively associated with psychosocial risk factors and negatively associated with psychosocial resources. 3) Pooling saliva samples prior to laboratory analysis were as reliable as arithmetic means for assessment of diurnal cortisol variation in a field research setting. 4) There was a positive association between circulating levels of MMP‐9 and saliva levels of cortisol, both diurnal peak level and evening level of cortisol. The observed associations between MMP‐9 and traditional cardiovascular risk factors, psychosocial factors, and saliva cortisol levels suggest a psychoneuroendocrinological pathway linking stress to plaque vulnerability and provide increased understanding of the association between psychosocial factors and CAD.
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| 6. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 7. |
- Huber, Daniel, 1980-
(författare)
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On secondary prevention after acute coronary syndrome : -what, when, and who
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCardiovascular disease, of which coronary heart disease constitutes the lion’s share, is the leading cause of premature morbidity and mortality worldwide. Management of the condition has evolved rapidly in recent decades, and mortality has more than halved in the western world. Because of intense research, solid evidence supports effective and inexpensive means of preventing disease progression. However, secondary prevention still yields disappointingly low success in meeting guideline-recommended risk factor targets. It is therefore vital to develop more effective risk factor management.AimsWe aimed to assess the feasibility of a nurse-led, telephone-based, secondary preventive intervention in an unselected population with acute coronary syndrome (ACS). Furthermore, we sought to evaluate the flexibility of the intervention to adapt to a change in guidelines. We also aimed to evaluate whether the intervention was more effective than usual care at improving risk factor levels for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) 12 months after discharge. Finally, we aimed to measure whether the intervention improved long-term adherence to statins.MethodsAll papers are based on the Nurse-based Age-independent Intervention to Limit Evolution of Disease after ACS (NAILED-ACS) trial. The NAILED trail has two arms, one after stroke/transient ischemic attack (NAILED-Stroke) and one after ACS (NAILED-ACS). All studies are based on NAILED-ACS aside from study II which includes both arms. The trial was an open, 1:1 randomized, controlled, parallel group trial that compared nurse-led telephone follow-up with medical titration (intervention) to a control group with follow-up by a general practitioner (control). All patients admitted to Östersund Hospital for ACS during 2010–2014 were eligible if available for preventive management by telephone. A baseline assessment was made at 1 month after discharge and thereafter every 12 months for at least 3 years. Feasibility was assessed among patients admitted until 31 January 2013, and predictors of exclusion and non-participation were identified. The performance of the intervention in implementing a guideline change was evaluated in patients with diabetes with both ACS and stroke as inclusion events after a change in LDLC target from <2.5 mmol/L to <1.8 mmol/L. LDL-C levels were compared between intervention and control patients before and after the guideline changed. Reasons for not reaching the target level were recorded. The outcomes of the intervention on BP and LDL-C were studied in patients admitted until 31 December 2013. We measured proportions reaching targets and levels of LDL-C and BP during the first 12 months of follow-up, with comparisons between the intervention and control groups. Adherence to statin treatment was measured in the entire study cohort, with at least 36 months of follow-up, with classification of reasons and analysis of predictors for both a first and a permanent discontinuation.ResultsOf 907 screened patients with ACS in the first study, 72.9% were included, and 11% declined participation. Among the 16.1% who were excluded, the predominant reasons were participation in other trial, dementia, and advanced disease. Non-included patients were significantly older, with more comorbidities, decreased functional capability, and lower level of education compared to included. Excluded and declining patients also had a reduced oneyear survival in comparison with included.Before the guideline changed, 96% of the 101 patients in the intervention group reached LDL-C <2.5 mmol/L compared to 70% of the 100 control patients (p<0.001). One year after target reduction to <1.8 mmol/L, the same proportions were 65% and 36%, respectively (p<0.001). The predominant reason for nonattainment of target in the intervention group was full-dose treatment; for the control group, it was that no medication adjustment was made. After medical titration, at 1 month (baseline), 94.1% in the intervention group achieved target for LDL-C (<2.5 mmol/L) compared to 68.4% in the control group. Mean LDL-C was 0.38 mmol/L lower in the intervention group (p<0.05 for both). At the 12-month assessment, 77.7% of the intervention group attained the LDL-C target compared to 63.2% of the control group, and mean LDL-C was 0.3 mmol/L lower among intervention patients (p<0.05 for both). In the intervention group, 91.9% achieved targets for systolic BP and 96.2% for diastolic BP after baseline titration compared to 65.6% and 82.0%, respectively, in the control group (p<0.05 for both). At 12 months, 68.9% in the intervention group reached the target for systolic BP and 88.1% for diastolic BP, compared to 63.7% and 82.8%, respectively, in the control group (p=0.125 and <0.05). Mean systolic BP was 7 mmHg lower and mean diastolic BP 4 mmHg lower in the intervention group after 1-month titration compared to controls. At 12 months, the mean systolic BP was 1.5 mmHg lower and mean diastolic BP 2.1 mmHg lower in the intervention group.In our assessment of adherence to statin treatment, 89.3% in the intervention group and 81.7% in the control group were adherent to treatment during a mean follow-up of 3.9 years (p<0.001). In the intervention group, 27.8% discontinued at least once during the period, compared to 20.8% in the control group (p<0.05). The main reason for a first discontinuation was avoidable in both groups: sideeffects without a compelling association with treatment. The main reason for permanent discontinuation was predominantly non-avoidable in the intervention group (advanced disease and dementia) but avoidable in the control group (sideeffects without a compelling association with treatment). Predictors for increased risk for discontinuation were female sex, and for a first event, inclusion in the intervention group. Predictors for reduced risk of non-adherence were ST elevation myocardial infarction as an including event, and for permanent discontinuation, inclusion in the intervention group.ConclusionA nurse-led telephone-based method for secondary prevention can encompass a large proportion of an ordinary ACS cohort. Compared to usual care, it is more adaptable to changes in treatment guidelines and leads to better achievement of major risk factor targets as well as improved medication adherence.
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| 8. |
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| 9. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 10. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
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