| 1. |
- Calais, Fredrik, 1971-
(author)
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Coronary artery disease and prognosis in relation to cardiovascular risk factors, interventional techniques and systemic atherosclerosis
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Aim: To evaluate the prognosis associated with location and severity of coronary and systemic atherosclerosis in patients with coronary artery disease (CAD) in relation to risk factors and interventional techniques.Methods: The thesis comprised six longitudinal studies based on three patient cohorts: The Swedish Coronary Angiography and Angioplasty Registry, the Västmanland Myocardial Infarction Survey, and the Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia study, to evaluate clinical outcome relative to coronary lesion location and severity, extracoronary artery disease (ECAD), intervention techniques, and leisuretime physical inactivity (LTPI).Results: Stent placement in the proximal left anterior descending artery (LAD) was more often associated with restenosis than was stenting in the other coronary arteries. The use of drug-eluting stents in the LAD was associated with a lower risk of restenosis and death compared to baremetal stents. Thrombus aspiration in in the LAD during acute ST elevation myocardial infarction (MI) did not improve clinical outcome, irrespective of adjunct intervention technique. Clinical, but not subclinical, ECAD was associated with poor prognosis in patients with MI. Longitudinal extent of CAD at the time of MI was a predictor of ECAD, and coexistence of extensive CAD and ECAD was associated with particularly poor prognosis following MI. Self-reported LTPI was associated with MI and all-cause mortality independent of ECAD.Conclusions: Drug-eluting stents, but not thrombus aspiration, improved prognosis following percutaneous coronary intervention in the proximal LAD. Self- reported LTPI, clinical ECAD, and systemic atherosclerosis defined groups with poor prognosis after MI.
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| 2. |
- Djekic, Demir, 1989-
(author)
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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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Doctoral thesis (other academic/artistic)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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| 3. |
- Andersson, Tommy, 1970-
(author)
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Atrial fibrillation and cause of death, sex differences in mortality, and anticoagulation treatment in low-risk patients
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Background: Atrial fibrillation (AF) is the most common arrhythmia but information on cause of death in patients with AF is sparse, and whether individuals at low risk of cerebral infarction (CVL) should receive antico-agulant medication is controversial. Studies of sex differences with respect to mortality risk have shown conflicting results.Methods: Data were obtained from Swedish National Registers. In Study I, there were 272 186 AF patients and matched controls and in Studies II and III, 9519 AF patients and no other diagnosis and matched controls. Study IV compared treatment with warfarin to no treatment in 48 433 patients with AF. Hazard ratio (HR) was calculated with 95% confidence intervals and outcome rates as number per 1000 person-years.Results: Ischemic heart disease (IHD) was the most common underlying cause of death and was present in 40.2% of AF patients at a HR of 1.7 (1.4-2.1). CVL/stroke was a cause of death in 13.1%, HR 2.7 (1.8-4.0). Among underlying and contributing causes of death, the most common diagnoses were IHD in 43.5%, HR 1.7 (1.4-2.0) and heart failure in 33.1%, HR 2.9 (2.2-3.7). The HRs for mortality in females with AF in age categories ≤65, 65-74, and 75-85 were 2.15, 1.72, and 1.44, and for males 1.76, 1.36, and 1.24. The rates of mortality in females with AF in age categories 55-64, 65-74, and 75-85 were 6.2, 20.7, and 57.3, and for males 8.5, 27.3, and 64.5. In patients 65-74 years, females with a CHA2DS2-VASc score of 2, and males with a score of 1 receiving warfarin treatment showed a significantly reduced risk of cerebral infarc-tion/stroke, HR 0.46 (0.25-0.83) for females and for males, HR 0.39 (0.21-0.73).Conclusions: Most common causes of death in AF patients were CVL/stroke, heart failure, and IHD. HR of mortality in patients with AF was higher in females than in males but absolute risk was higher in males with AF compared to females with AF. Anticoagulant therapy was benefi-cial in patients ≥65 years, regardless of the CHA2DS2-VASc score.
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| 4. |
- Arinell, Karin, 1982-
(author)
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Immobilization as a risk factor for arterial and venous thrombosis
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Aim: Immobilization and a sedentary lifestyle are correlated with an elevated risk of both arterial and venous thrombosis. The goal of this research was to investigate whether markers associated with cardiovascular disease risk are altered during long term immobilization in a human model and in the brown bear, which survives annual cycles of long-term immobilization.Methods: In study populations assigned to 20-60 days of strict head-down-tilt bed rest 24h a day, we analysed blood levels of the emerging cardiovascular disease marker cystatin C, soluble markers of in vivo platelet activation P-selectin and PDGF-BB, and platelet aggregation. Blood samples were taken from free-ranging brown bears in summer and again during hibernation for analysis of lipid profile and platelet aggregation. Histological examination was performed on the left anterior descending coronary artery and aortic arches of bears harvested during the hunting season.Results: During prolonged bed rest in humans, levels of cystatin C and platelet aggregation remained unchanged, but we observed a significant decrease in platelet activation markers. Brown bear plasma lipids were elevated during hibernation compared with the active state and cholesterol levels were generally considerably higher than normal human values. The arterial specimens showed no signs of atherosclerosis. Platelet aggregation was halved during hibernation compared to the active state.Conclusions: Long-term immobilization has effects on several cardiovascular risk factors in both humans and bears. Increased knowledge and understanding of the protective mechanisms that allows the brown bear to survive repeated periods of immobilization could contribute to new strategies for prevention and treatment of cardiovascular disease in humans.
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| 5. |
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| 6. |
- Djekic, Demir, 1989-, et al.
(author)
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Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study
- 2020
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In: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 9:18, s. e016518-e016518
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Journal article (peer-reviewed)abstract
- Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4-week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4-week washout period. The primary outcome was difference in oxidized low-density lipoprotein cholesterol (LDL-C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short-chain and branched-chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL-C (-2.73 U/L), total cholesterol (-5.03 mg/dL), LDL-C (-3.87 mg/dL), and body weight (-0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l-carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL-C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL-C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL-C observed with the VD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02942628.
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| 7. |
- Djekic, Demir, 1989-, et al.
(author)
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VEgetaRian Diet in patients with Ischemic heart disease (VERDI) : an open-label, randomized, prospective, cross-over study
- 2019
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 40:Suppl. 1, s. 3819-3819
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Journal article (other academic/artistic)abstract
- Background: A vegetarian diet (VD) in patients diagnosed with ischemic heart disease (IHD) may reduce future cardiovascular risk.Purpose: The study hypothesis was that patients diagnosed with IHD can benefit from a VD assessed by multiple risk markers for this type of disease.Methods: In a crossover study patients diagnosed with IHD, treated by percutaneous coronary intervention and on optimal medical therapy were randomly allocated to a 4-week intervention with ready-made (lunch and dinner) isocaloric VD or meat diet (MD). The primary outcome was change in oxidized low-density lipoprotein cholesterol (LDL-C) levels. Secondary outcomes were difference in changes of blood lipids, weight, body mass index (BMI), blood pressure, heart rate, glycated haemoglobin (HbA1c), number of participants reaching guideline target values, quality of life, gut microbiota, and trimethylamine N-oxide between the two interventions.Results: 31 participants were recruited (median age: 67 years, male sex: 93.5%). Significant between-intervention differences (VD vs MD) were found in oxidized LDL-C (-2.73 U/L; p=.015), total cholesterol (TC) (-0.13 mmol/L, p=.01), LDL-C (-0.10 mmol/L; p=.02), weight (-0.67 kg, p=.008) and BMI (-0.21 kg/m2, p=.009). After VD, numerically more subjects reached guideline LDL-C target values (87% vs 77%) but this did not reach statistical significance (p=.07). During VD intervention the diet led to a significant reduction in oxidized LDL-C, TC, LDL-C, HDL-C, ApoB, and ApoB/ApoA1 ratio.Conclusions: Our results suggest that in patients with IHD a VD compared to a MD, lowers oxidative stress, improves lipid profile and lowers BMI.
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