| 1. |
- Dahlén, Elsa, 1975-
(författare)
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Markers of subclinical atherosclerosis and arterial stiffness in type 2 diabetes
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Type 2 diabetes is a common disease with increased mortality and morbidity due to cardiovascular disease (CVD). This thesis is based on three studies that evaluated traditionally used and emerging risk markers to identify individuals with high-risk of developing CVD in middle-aged men and women with type 2 diabetes. One study was conducted to compare the equivalence between two different ultrasound techniques to measure intima-media thickness since IMT was used to evaluate subclinical atherosclerosis as a surrogate endpoint.Methods: Data from the cohort study, cardiovascular risk in type 2 diabetes – a prospective study in primary care (CARDIPP) was used in paper I, III and IV. In paper I, baseline data from the first 247 subjects was analysed. Associations between traditionally measured lipids, apolipoproteins, glycaemic control and low-grade inflammation and IMT were analysed.In paper III, the full baseline cohort, with data from 761 subjects from the CARDIPP study was cross-sectionally analysed regarding correlations between abdominal obesity measured as waist circumference (WC) and sagittal abdominal diameter (SAD), inflammatory markers and IMT and pulse wave velocity (PWV). In paper IV, the associations reported in paper I and III were prospectively investigated with data from the first year of follow-up four years after the baseline investigations in CARDIPP-revisited.In paper II a study was performed on 24 young healthy subjects, both men and women. IMT was measured in the common carotid artery (CCA) and in the abdominal aorta (AA), by two skilled ultrasonographers, with 2 different ultrasound techniques in a randomised order.Results: ApoB/apoA-I ratio (r=0.207, p=0.001), apoB (r=0.166, p=0.009) and non HDLcholesterol (nHDL-c) (0.129, p=0.046) correlated with IMT.In CCA IMT was equivalent using B-mode- and M-mode respectively. However in AA, IMT was 11.5% thicker using B-mode.Abdominal obesity were significantly correlated with; IL-6 and CRP (both p<0.001, WC and SAD respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001 WC and SAD respectively). Adjusting for age, sex, treatment with statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, SAD (p=0.047) but not WC, remained associated with IMT.There were significant correlations between apoB (r=0.144, p=0.03) and CRP (r=0.172, p=0.009) measured at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r=0.130, p=0.049), WC (r=0.147, p=0.027) and SAD (r=0.184, p=0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p=0.036).Conclusions: There was a significant association between apoB/apoA-I ratio and IMT. The association was independent of conventional lipids, CRP, glycaemic control and use of statins. Both SAD and WC were associated with inflammation, atherosclerosis and arterial stiffness. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC. Prospectively; apoB and CRP, but not LDL-cholesterol predicted increased subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.The two different ultrasound techniques, B-mode and M-mode, measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.
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| 2. |
- E:son Jennersjö, Pär, 1956-
(författare)
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Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundType 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes.MethodsData from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of sagittal abdominal diameter.ResultsPaper 1:Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure.Paper 2:The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV.Paper 3:At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up.Paper 4:Low vitamin D levels were associated with significantly increased risk for premature mortality in men with type 2 diabetes. High levels of parathyroid hormone were associated with significantly increased risk for premature mortality in women with type 2 diabetes. These relationships were still statistically significant also when two other well-established risk markers for mortality, PWV and carotid intima-media thickness, were added to the analyses.ConclusionsAmbulatory blood pressure recording can by addressing the issue of diurnal blood pressure variation, explore early cardiovascular organ damage and microvascular complications that goes beyond effects of standardised office blood pressure measurements. Pedometer-determined physical activity may serve as a surrogate marker for inflammation and subclinical organ damage in patients with type 2 diabetes. There is novel support for the durable vascular protective role of a high level of daily physical activity, which is independent of BMI and systolic blood pressure. The use of pedometers is feasible in clinical practice and provides objective information not only about physical activity but also the future risk for subclinical organ damage in middle-aged people with type 2 diabetes. Our results indicate that low vitamin D levels in men or high parathyroid hormone levels in women give independent prognostic information of an increased risk for total mortality.
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| 3. |
- Gjessing, Kristian, 1967-
(författare)
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Impact of medical and non-medical Factors on Quality and Costs in Primary Care : A Conscious Look at Subconcious Processes
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background / IntroductionPhysicians and patients may be influenced by more than just the medical facts of the situation at hand. The physician is a part of the sociocultural environment and is under influence of this. The physician could be afraid of making mistakes and thus choose the safest option. In addition, economic considerations may apply. The perceived continuity or quality of the communication may also influence medical decision-making. Patients may not think about what allergens they are exposed to. Differences in socioeconomy or perceived morbidity may influence the patient's or their family’s desire to see the doctor or to use medications like antibiotics.Material and MethodsIn Paper 1, referrals from two Primary Healthcare centers in Norway were compared to each other and to the other referrals that were received by the local hospital. In Paper 2, Influenza-Like Illness (ILI) for children 2-12 years old was monitored for 7 years, and costs of treatment and parental absence due to ill children were calculated using real numbers. In Paper 3, the number of antibiotic prescriptions was compared to the patient’s socioeconomic background, to investigate possible inequalities. Paper 4 compares asthma and atopy incidence to the number of antibiotic prescriptions, to investigate if asthma patients are more often treated with antibiotics than nonasthma patients are. The analyses are based on regional healthcare data and the prospective ABIS study.ResultsPaper 1 showed that locum doctors and regular General Practitioners had the same referral rates, but the locum doctors had a distribution of diagnoses that differed significantly from the regular GPs and from the other referrals.Paper 2 showed that parental absence due to children with ILI follows the seasonal influenza pattern closely. The main burden of consultations and costs is carried by Primary Care.Paper 3 showed that parent-reported infectious morbidity at age 5, is associated with a higher number of antibiotic prescriptions in later childhood (5-14 years). Family income is a factor, where children from Q1 (wealthiest) receive significantly fewer antibiotics than children from Q3-Q5.Paper 4 found that asthma/ fur allergy at age 5 was associated with more antibiotic prescriptions in later childhood, but that wide-spectrum antibiotics are rarely used. Doctors seem to adhere to national and regional guidelines.ConclusionsPrimary care physicians seem to be affected by their grade of continuity and length of employment in their referral diagnosis distribution. Influenza-like illness in children carries a substantial cost in terms of loss of production, healthcare encounters, and personal suffering for vulnerable individuals. Parents’ perceptions of morbidity seem to influence antibiotic demand in children, along with socioeconomic factors. Children with asthma or airway allergies seem to receive more antibiotic prescriptions, possibly due to increased infectious vulnerability or to allergic exposure unknown to the doctor.
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| 4. |
- Guldbrand, Hans, 1950-
(författare)
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Trials of Diets for Treatment of Diabetes : A comparison of diets for treatment of type 2 diabetes, aspects on long and short term effects
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundType 2 diabetes is a common disease and the prevalence has increased in large parts of the world. In treatment of diabetes the type of diet is of great importance considering metabolic factors such as glucose level and blood lipids. Which diet that is most beneficial to avoid diabetic complications has been heavily debated in recent decades. This thesis is based on two clinical studies designed to compare the effects of different macronutrients.MethodsA clinical trial was designed to compare a low-carbohydrate diet (LCD) to a low-fat diet (LFD) in treatment of patients with type 2 diabetes. Sixty-one patients at two health care centres were included and randomized to get advice to eat a LCD or a LFD. The LCD had an energy content where 50 energy percent (E%) where from fat, 20 E% from carbohydrates and 30 E% from protein. For the LFD the nutrient composition was similar to what is traditionally recommended for treatment of type 2 diabetes in Sweden. Metabolic factors, anthropometrics and questionnaires were analysed.To study postprandial effects a trial was designed to compare three different diets. Twentyone patients with type 2 diabetes were included to in randomized order test the three types of diets on separate test days. On each test day the patients were served breakfast and lunch and blood samples were taken at six times these days. Glucose, lipids and hormones were analysed.ResultsThere were equal weight reduction in the two groups in the first trial during the two-year study period. At six month when compliance was good according to diet-records, the glucose level (HbA1c) was lowered and the HDL-cholesterol was increased in the LCD group. The inflammatory markers IL-6 and IL-1Ra were significantly lower in the LCD group than in the LFD group. At 12 months the physical function, bodily pain and general health scores improved within the LCD group only.In the second trial the postprandial glucose and insulin levels were lower on the LCD compared to the LFD. However, the LCD resulted in a tendency to higher postprandial triglyceride levels. The Mediterranean type of diet with all energy intake at lunch resulted in a more pronounced insulin response and a glucose level at lunch similar to that of the low-fat diet. The increase-ratio of insulin correlated to the elevation of the incretin glucose-dependent insulinotropic peptide (GIP).ConclusionsIn the two-year study we found benefits for the LCD group regarding glucose control and insulin doses. Furthermore, only the LCD was found to improve the subclinical inflammatory state and there were some aspects of improved well-being in this group. Aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk factors compared with the traditional LFD and this approach could constitute a treatment alternative.In the postprandial state, the LCD induced lower insulin and glucose excursions than the LFD but at the same time a tendency of higher triglycerides. The long-term significance needs to be further examined. The accumulation of caloric intake from breakfast to lunch to a single large Mediterranean-style lunch-meal in type 2 diabetes might be advantageous from a metabolic perspective.
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| 5. |
- Nord, Magnus, 1967-
(författare)
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Proactive Primary Care for Older Adults at High Risk of Hospital Admission
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Demographic change is leading to a higher proportion of older adults in most parts of the world. A minority of older adults have poor health, but this group has high care needs due to frailty and/or multimorbidity. Guidelines for the management of frailty emphasise early detection of frailty and recommend comprehensive care approaches in primary care, but the evidence for these interventions is low. To provide effective and individualised care, the health system needs to identify these patients and develop proactive interventions to improve quality of life and avoid treatments that are of no benefit to the individual. The aim of this thesis was to study the effects of a proactive primary care working model in which vulnerable older adults were identified and received individually tailored care, using an adaptation of comprehensive geriatric assessment (CGA). Methods: A pragmatic controlled trial was conducted in 19 primary care practices in Sweden from 2017 to 2020. A predictive model, using electronic medical records to assess the risk of hospital admission, selected participants at high risk. Participants in the intervention practices were offered a comprehensive geriatric assessment in their primary care practice and subsequent follow-up by a team consisting of a nurse and the patient's doctor. A new CGA tool - PASTEL (Primary care ASsessment Tool for Elders) was used for assessment and care planning. The primary outcome for the intervention was hospital care days and secondary outcomes were hospital care episodes, mortality, outpatient visits, healthcare costs and cost-effectiveness. The outcomes were adjusted for age, sex and risk score and ana-lysed according to intention-to-treat. The predictive model was validated, and performance was assessed using the C-statistic. Focus group interviews were conducted to explore primary care nurses' and doctors' experiences with the new tool PASTEL. Results: 1304 older adults were included in the trial. The mean age was 82.2 years, 51% were female. During the follow-up period of 24 months, the relative risk reduction of hospital care days in the intervention group was - 22% (CI 95% = -35% to - 4%, p = 0.02) compared with usual care. There was no significant difference in mortality and outpatient visits. The reduction in healthcare costs was - € 4324 (- € 7962 to - € 686, p = 0.02). The intervention was cost-effective compared with usual care, mainly due to lower costs.The predictive model had an AUC of 0.69 (CI 0.68- 0.70). Primary care staff considered PASTEL valuable and feasible in the primary care context.In conclusion, the results of this thesis indicate that vulnerable older adults at risk of hospitalisation can be identified by a predictive model. Proactive intervention with a comprehensive geriatric assessment adapted to pri-mary care can reduce the need for hospital care. Future studies in similar contexts are needed to determine whether these results are generalisable.
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| 6. |
- Rådholm, Karin, 1976-
(författare)
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Cardiovascular risk factors in elderly : With special emphasis on atrial fibrillation, hypertension and diabetes
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe part of the population that belongs to the oldest-old (ages 80 years or older) increases rapidly, worldwide. Cardiovascular disease (CVD) is the leading cause of death and disease burden globally. Multimorbidity is common in old age and stroke, diabetes mellitus (DM) and atrial fibrillation (AF) are strongly associated with age. Cardiovascular risk factors are well studied and documented in younger and middle ages, but not as well in old and frail individuals. Therefore, preventive treatment choices are mostly based on evidence for younger patients. The aim of this thesis was to explore age and other aspects of cardiovascular risk factors; AF, hypertension and DM, in relation to comorbidity, cardiovascular outcome and mortality.MethodsThis thesis was based on four different studies:The ELSA85 study of 85 years old in Linköping, SwedenThe international, multicentre, randomised controlled INTERACT2 trial of spontaneous intracranial haemorrhage (ICH), mean age 64 years.The prospective SHADES study of nursing home residents, mean age 85 years.The prospective, national SWE-diadep study of dispensed antidiabetics, antidepressantsand prevalent myocardial infarction (MI) in 45-84 years old.Data was obtained from questionnaires (ELSA85, INTERACT2), medical records and medical examination (ELSA85, INTERACT2, SHADES), and national registers (SWE-Diadep).ResultsThe ELSA85 study showed that 16% (n=53) had an ECG showing AF. There was an increased hazard ratio (HR) for all-cause mortality in participants with AF at baseline, at 90 years of age (HR 1.59, 95% [Confidence Interval] CI 1.04-2.44) adjusted for sex. This increase in HR did not persist when adjusted for congestive heart failure (CHF). In the INTERACT2 study, increasing age was associated with increasing frequency of death or dependency (odds ratio [OR] 4.36, 95% [CI] 3.12-6.08 for >75 years vs <52 years, p value for trend <0.001). The SHADES study showed that participants with Systolic blood pressure (SBP) <120 mmHg had an increased HR for mortality (1.56, 95% CI, 1.08–2.27; p=0.019) but there were no differences between SBP groups 140–159 mmHg and ≥160 mmHg compared with the reference group SBP 120–139 mmHg. SBP decreased during the prospective study period. In the SWE-diadep study, individuals with antidiabetics and antidepressants combined had a greater HR for MI compared to the reference of no antidiabetics or antidepressants, mostly so in women aged 45-64 years (HR 7.4, 95% CI: 6.3-8.6).ConclusionRisk factors for CVDs in elderly differ from cardiovascular risk factors in middle aged individuals an
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| 7. |
- Samefors, Maria, 1980-
(författare)
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Aspects of Vitamin D Deficiency in Elderly People in Nursing Homes and in Patients with Type 2 Diabetes : with Emphasis on Mortality, Cardiovascular Morbidity and Mental Health
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundInstitutionalised elderly people living in northern latitudes may be at elevated risk for vitamin D deficiency. They are recommended to take oral vitamin D supplements, but the main source of vitamin D is sunlight. Previous studies have shown an association between low levels of vitamin D and several diseases, but important knowledge about vitamin D in elderly people in nursing homes and in patients with type 2 diabetes is lacking. The aims of this thesis were to study aspects of vitamin D deficiency in these two populations and to explore whether low vitamin D levels were associated with mortality, cardiovascular morbidity and mental health. Also, we aimed to examine whether an intervention with encouragement to spend time outdoors during summer could increase vitamin D levels in the elderly in nursing homes.MethodsThe present thesis is based on four papers. Papers I and IV are confined to nursing home residents >65 years. Paper I is based on data from SHADES (The Study of Health and Drugs in the Elderly). Paper IV is based on the study Sunlight and Vitamin D in Older People in Nursing Homes. Papers II and III are based on data from CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes—a Prospective Study in Primary Care), with patients with type 2 diabetes aged 55-66 years. Papers I-III were prospective observational cohort studies and Paper IV was a cluster randomised intervention trial.In Paper I, serum 25-hydroxyvitamin D3 (25(OH)D3) was analysed on three occasions. The vital status of the subjects was ascertained and hazard ratios (HRs) for mortality according to baseline 25(OH)D3 quartiles (Q) were calculated.In Paper II, serum 25(OH)D3 was analysed at baseline. HRs for the first myocardial infarction, stroke or cardiovascular mortality according to 25(OH)D3 were calculated.In Paper III, serum 25(OH)D3 was analysed at baseline. The SF-36 questionnaires measuring vitality and mental health were administered at baseline and after four years.In Paper IV, the intervention group was encouraged to go outside for 20-30 minutes every day for two months during the summer of 2018. Before and after the summer, serum 25(OH)D was analysed and SF-36 questionnaires measuring vitality and mental health were administered.ResultsIn Paper I, 80% of the participants had 25(OH)D3 < 50 nmol/l. Vitamin D deficiency was associated with an increased mortality risk. Compared with Q4 (25(OH)D3 >48 nmol/l), the HR (with a 95% confidence interval (CI)) for mortality was 2.02 (1.31-3.12) in Q1 (25(OH)D3 <29 nmol/l) (p<0.05), 2.03 (1.32-3.14) in Q2 (25(OH)D3 30-37 nmol/l) (p<0.05) and 1.6 (1.03-2.48) in Q3 (25(OH)D3 38-47 nmol/l) (p<0.05).In Paper II, serum 25(OH)D3 was inversely associated with the risk of cardiovascular morbidity and mortality. The HR per nmol/l was 0.98 (95% CI: 0.96-0.99) (p=0.001), when adjusted for age, sex and season.In Paper III, serum 25(OH)D3 was inversely associated with poor mental health at baseline. The odds ratio (OR) for 10 nmol/l increase in 25(OH)D3 was 0.90 (95% CI: 0.83-0.96) (p=0.003), but not at follow-up (p>0.05). Serum 25(OH)D3 was not associated with vitality at baseline (p>0.05), nor at follow-up after adjustments.In Paper IV, the 25(OH)D levels increased significantly in the intervention group during the summer: from a median (interquartile range (IQR)) of serum 25(OH)D of 42.5 (23.0) nmol/l to 53.5 (33.0) nmol/l (p=0.011). The 25(OH)D levels increased in the control group as well, but the increase was not significant. The intervention group reported better mental health after the summer compared to before the summer (p=0.015), unlike the control group.ConclusionsLow vitamin D levels were associated with increased mortality in elderly people in nursing homes, and with cardiovascular morbidity/ mortality and poor mental health in patients with type 2 diabetes. From our studies, we cannot draw conclusions about causality. The results indicate that the vitamin D levels give prognostic information. Active encouragement to spend time outdoors during summer improved the vitamin D levels and mental health in elderly people in nursing homes, and such activity could be considered as a complement to oral vitamin D supplementation in the summer.
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| 8. |
- Vavruch, Camilla
(författare)
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Leptin and the Intersection of Cardiovascular Disease, Metabolism, and Adipose Tissue
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- According to the World Health Organization, cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels, and it is the leading cause of death worldwide. The risk factors for CVD are divided into two major classes: non-modifiable (age, gender, family history) and modifiable (including tobacco use, type 2 diabetes mellitus (T2DM), physical inactivity, unhealthy diet, abdominal obesity, high cholesterol, dyslipidemia, and stress). Because CVD is a major cause of mortality and morbidity, new and clinically useful biomarkers of cardiovascular risk are of essence. Since obesity is a risk factor for CVD, new ways to achieve weight loss are also important. In this thesis, the focus is on leptin, a metabolic hormone with a pivotal function in the balance of appetite and satiety, and inducing weight loss. The adipose tissue releases leptin, with plasma levels of leptin reflecting the total adipose mass. Since it is related to both fat mass and cardiovascular risk, and is pro-inflammatory, it has been studied as a potential link between obesity, inflammation, hypertension, and vascular function. In paper I, we aimed to see if repeated cold exposure increased metabolic rate and/or brown adipose tissue (BAT) volume in humans. Out of 28 recruited participants, we allocated 16 to expose themselves to cold for one hour every day for six weeks, while 12 were controls, instructed to avoid cold exposure. Through magnetic resonance imaging, we found that supra-clavicular BAT volume had increased in an on-treatment analysis of the cold exposure group. In paper II, we used baseline data from 720 participants in “Cardiovascular Risk factors In Patients with Diabetes—a Prospective study in Primary care” (CARDIPP), all of whom had T2DM and were 55-66 years old at recruitment. We followed patients for incidence of ischemic heart disease (IHD) mortality and morbidity for 4-7 years, using the national Swedish Cause of Death and Hospitalization Registries. Our study showed that serum leptin levels related positively to the hazard ratio in both men and women, and predicted IHD independently of age, HbA1c, BMI, systolic blood pressure, and LDL/HDL-cholesterol ratio. This supports the use of serum leptin in patients with T2DM to add independent prognostic information in terms of IHD. When adding pulse wave velocity (PWV) and intima-media thickness to the model as markers of arterial stiffness, the finding of increased risk of IHD related to leptin levels remained statistically significant in men, but not in women. In paper III, we aimed to discover novel associations between leptin and circulating proteins, to possibly link leptin with the development of CVD in patients with T2DM. Using proximity extension assay, we investigated associations between 88 plasma proteins in the CARDIPP population. We replicated the associations passing the significance threshold in patients with T2DM in an independent cohort and found that adipocyte fatty acid binding protein (A-FABP) was significantly associated with leptin in both cohorts, more so in men than women. A-FABP can be found in white adipocytes and macrophages, and some studies have identified it as a circulating biomarker for metabolic syndrome, T2DM, and cardiovascular events. Finally, in paper IV, we analyzed data from 1 658 men and 1 678 women aged 50 to 65 when included in “The Swedish CardioPulmonary bioImage Study” (SCAPIS), focusing on leptin and its possible correlation with PWV. In bivariate correlations, we found log transformed leptin, and inflammatory markers IL-6, IL-18, and CRP, were all correlated in both men and women. In a multivariable linear regression, log transformed leptin correlated positively with PWV, independently of home blood pressure, smoking, non-HDL, BMI, T2DM, and IL-6, IL-18, and CRP. This suggests it may be possible to use leptin as a marker for PWV and arterial stiffness.In conclusion, this thesis provides new insights into leptin and its potential associations with other circulating proteins, and its connection to cardiovascular disease and inflammation, both in patients with T2DM and in healthy subjects. It also provides more insight into brown adipose tissue.
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| 9. |
- Vergara, Marta, 1976-
(författare)
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Impact of different interventions on cardiovascular risk factors
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity and related complications such as diabetes mellitus type 2 (T2DM) and cardiovascular events, are a growing major health problem worldwide. Achieving a negative energy balance by increasing physical activity in combination with reduced caloric intake, is the most common approach in weight reduction strategies, something that is difficult to maintain in the long term. Other possible strategy to increase energy expenditure could be enhancing resting metabolic rate (RMR) by increasing energy consumption in muscle tissue.Regular exercise is often recommended as part of the treatment and prevention of cardiovascular disease (CVD) and it is expected to ameliorate risk factors associated with the metabolic syndrome, such as glucose and insulin metabolism, lipid profile and blood pressure. However, extreme exercise performance seems to have potential unbeneficial effects on inflammation, oxidation, and cardiac health. We intended to study the impact of a more common way of exercise in different cardiovascular risk factors and how natural antioxidants, protein supplementation or hypercaloric diet could influence the results. In patients with already established T2DM, it is important to find new and easy to manage markers for CVD, as it is the main cause of morbidity and mortality in this patient group. Even if quality of life (QoL) is strongly related to CVD in patients with T2DM, it is still not incorporated in routinary clinical assessments.Paper I: Resistance training (RT) performed by healthy men for three months, increased lean body-mass and RMR. The increase of RMR was dependent on both an increase in muscle mass and a higher RMR per kg of muscle tissue. Even if it was equally efficient to combine training with whey protein supplementation or with increased energy intake, hyperalimentation with an extra intake of a fast-food resulted in an impaired cardiovascular profile, with reduced insulin sensitivity and higher ApoB levels. Thus, regularly performed RT could be helpful in the treatment of obesity by increasing RMR.Paper II: Regularly running 5 km for 4 weeks resulted in a positive outcome, leading to lower insulin and triglyceride levels, higher HDL cholesterol, and a tendency to lower inflammation when compared with a period of minimal physical activity. However, Troponin-T, marker of myocardial injury, was detectable after a 5 km race at maximal speed in almost half of the races. Consuming blueberries showed a cardioprotective effect, blunting troponin-T release and improving the lipid profile. Less positive was the increase of fasting glucose in consumers of blueberries, which could be an indirect effect of concomitant diet. Paper III: Running 5 km at maximal speed may not be as advantageous for cardiovascular health as expected, at least when looking at the acute effects of a single race in healthy young individuals. A relative short race seemed to reduce insulin sensitivity and despite increased insulin levels, glucose was higher directly after the race compared with a resting day. Indeed, we found elevated cortisol and Troponin-T levels after the races, which suggests that running a distance that is common among recreational runners, may not be fully advantageous for cardiovascular health when performed in a strenuous way.Paper IV: We investigated if selected questions regarding the domains "general mental health and well-being" and "vitality", from QoL measurement instrument SF-36, could predict cardiovascular events and death in patients with T2DM in primary care. These two questions: "During the last 4 weeks, did you feel full of pep?" and "During the last 4 weeks, did you have a lot of energy?" were shown to be markers for major adverse cardiovascular events (MACE) independently of traditional vascular risk factors as well as arterial stiffness.
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| 10. |
- Wijkman, Magnus
(författare)
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Acute, ambulatory and central blood pressure measurements in diabetes
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In patients with diabetes, high blood pressure is an established risk factor for cardiovascular disease. The aim of this thesis was to explore the associations between blood pressure levels measured with different techniques and during different circumstances, and the degree of cardiovascular organ damage and subsequent prognosis in patients with diabetes.Methods: We analysed baseline data from patients with type 2 diabetes who participated in the observational cohort study CARDIPP (Cardiovascular Risk factors in Patients with Diabetes – a Prospective study in Primary care), and longitudinal data from patients registered in the Swedish national quality registry RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive care Admissions). Patients in CARDIPP underwent nurse-recorded, 24-hour ambulatory and non-invasive central blood pressure measurements. Patients in RIKS-HIA had their systolic blood pressure measured upon hospitalisation for acute chest pain.Results: In CARDIPP, nearly one in three patients with office normotension (<130/80 mmHg) were hypertensive during the night (≥120/70 mmHg). This phenomenon, masked nocturnal hypertension, was significantly associated with increased arterial stiffness and increased central blood pressure. Furthermore, nearly one in five CARDIPP patients with office normotension had high central pulse pressure (≥50 mmHg), and there was a significant association between high central pulse pressure and increased carotid intima-media thickness and increased arterial stiffness. Among CARDIPP patients who used at least one antihypertensive drug, those who used beta blockers had significantly higher central pulse pressure than those who used other antihypertensive drugs, but there were no significant between-group differences concerning office or ambulatory pulse pressures. In CARDIPP patients with or without antihypertensive treatment, ambulatory systolic blood pressure levels were significantly associated with left ventricular mass, independently of central systolic blood pressure levels. When RIKS-HIA patients, admitted to hospital for chest pain, were stratified in quartiles according to admission systolic blood pressure levels, the risk for all-cause one-year mortality was significantly lower in patients with admission systolic blood pressure in the highest quartile (≥163 mmHg) than in patients with admission systolic blood pressure in the reference quartile (128-144 mmHg). This finding remained unaltered when the analysis was restricted to include only patients with previously known diabetes.Conclusions: In patients with type 2 diabetes, ambulatory or central blood pressure measurements identified patients with residual risk factors despite excellent office blood pressure control or despite ongoing antihypertensive treatment. Ambulatory systolic blood pressure predicted left ventricular mass independently of central systolic blood pressure. In patients with previously known diabetes who were hospitalised for acute chest pain, there was an inverse relationship between systolic blood pressure measured at admission and the risk for one-year all-cause mortality.
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