| 1. |
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| 2. |
- Andren, Ann, et al.
(author)
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Effects of treatment with oral appliance on 24-h blood pressure in patients with obstructive sleep apnea and hypertension : a randomized clinical trial
- 2013
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In: Sleep and Breathing. - : Springer Science and Business Media LLC. - 1520-9512 .- 1522-1709. ; 17:2, s. 705-712
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Journal article (peer-reviewed)abstract
- Continuous positive airway pressure treatment has been shown to lower blood pressure (BP) in patients with obstructive sleep apnea (OSA). The aims of the present pilot study were to evaluate the potential effects of oral appliance (OA) therapy on BP, to assess various outcome BP measures, and to inform sample size calculation. Seventy-two patients with OSA and hypertension were randomly assigned to intervention with either an OA with mandibular advancement (active group) or an OA without advancement (control group). Before and after 3 months of treatment, the patients underwent nocturnal somnographic registration and 24-h ambulatory BP monitoring. Among the various BP measures, the largest trend toward effect of OA treatment was seen in 24-h mean systolic BP with a 1.8 mmHg stronger BP reduction in the active group compared with controls. A stronger trend toward effect was seen in a subgroup with baseline ambulatory daytime mean systolic BP > 135/85 mmHg where the mean systolic BP fell, on average, 2.6 mmHg. Additional exclusion of patients with baseline apnea hypopnea index (AHI) a parts per thousand currency sign15 gave a significant reduction in mean systolic BP of 4.4 mmHg (P = 0.044) in the active group compared with controls. In patients with OSA and hypertension, OA treatment had a modest trend toward effect on reducing BP. A stronger trend toward treatment effect was seen after excluding patients with normal baseline ambulatory BP. Additional exclusion of patients with baseline AHI a parts per thousand currency sign15 showed a significant treatment effect. Data to inform sample size for an adequately powered randomized study are provided.
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| 3. |
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| 4. |
- Andrén, Cecilia M., et al.
(author)
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Response of Gammarus pulex and Baetis rhodani to springtime acid episodes in humic brooks
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Other publication (other academic/artistic)abstract
- Although the acid load has decreased throughout Scandinavia, episodic acidification continues to affect stream biology by temporarily decreasing pH levels and mobilising aluminium. These events are becoming more common as climate change renders more frequent and intense storm floods. The transient acidity can reduce fish populations, but fish food resources can also be impaired because macro-invertebrates are affected. In this in-stream study, two salmonid prey organisms (Gammarus pulex and Baetis rhodani) were exposed to snowmelt in six humic brooks with a natural gradient of pH and inorganic monomeric Al (Ali). We hypothesise that there are thresholds for acid toxicity that can be defined by mortality and changes in body elemental content. Mortality was observed and the whole body content of base cations (BC, i.e., Ca, Mg, Na and K) and metals (Al, Fe, Zn and Mn) were determined. Both species began to die and the total bodily BC content decreased as the pH levels decreased and the Ali concentrations increased. In contrast to what has been observed for fish gills, no accumulation of Al was observed. The invertebrate body Na content decreased when the pH level decreased, which indicated that the osmoregulation in both species was affected. The Ca content in G. pulex and the Mg content in B. rhodani diverged from the general BC-pattern by increasing when the pH level decreased. The mortality increased drastically at pH <6.0 and Ali >15 μg/L for G. pulex and at pH <5.7 and Ali >20 μg/L for the somewhat less sensitive B. rhodani. Although Ali is tightly correlated to pH, the local Al availability in soil and bedrock also affect the Al release and toxic Ali episodes can consequently arise in some catchment areas. The estimated values can be used as water quality thresholds to adjust lime dose because both Ali and pH levels have to be balanced to prevent harm in recovering stream ecosystems.
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| 5. |
- Andrén, Cecilia M., et al.
(author)
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Response of Gammarus pulex and Baetis rhodani to springtime acid episodes in humic brooks
- 2013
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 463, s. 690-699
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Journal article (peer-reviewed)abstract
- While chronic acidification of water bodies has been steadily decreasing, episodic acidification continues to affect stream biology by temporarily decreasing pH and mobilizing aluminum. These events are becoming more common as climate change renders more frequent and intense storms and flooding. Throughout Scandinavia, the effects of acidification have been mitigated by liming since the 1980s, but remediation efforts can now be reduced. While transient acidity may reduce fish populations, also other species in streams are affected. In this in-stream study, two macro-invertebrates (Gammarus pulex and Baetis rhodani), both known as salmonid prey organisms, were exposed to snowmelt in six humic brooks with a natural gradient of pH and inorganic monomeric Al (Al-i). We hypothesize that acid toxicity thresholds can be defined using lethal (mortality) and sublethal (changes in body elemental content) metrics. Periodic observations were made of mortality and whole body concentrations of base cations (BC: Ca, Mg, Na and K) and metals (Al, Fe, Zn and Mn). Mortality increased dramatically at pH < 6.0 and Al-i > 15 mu g/L for G. pulex and at pH < 5.7 and Al-i > 20 mu g/L for B. rhodani. No accumulation of Al was found. The invertebrate body Na concentration decreased when pH dropped, suggesting that osmoregulation in both species was affected. In contrast to general BC pattern, Ca concentration in G. pulex and Mg concentration in B. rhodani increased when pH decreased. Although Ali strongly correlates to pH, the Al composition of soil and bedrock also influences Al availability, potentially contributing to toxic Al; episodes. The estimated values calculated in this study can be used to improve water quality criteria and as thresholds to adjust doses of lime compared to old recommendations in ongoing liming programs. Such adjustments may be critical since both Ali and pH levels have to be balanced to mitigate damage to recovering stream ecosystems.
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| 6. |
- Andrén, Cecilia M., 1964-
(author)
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Toxicity of Inorganic Aluminium in Humic Streams
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Aluminium (Al) has been recognised as a main toxic factor alongside pH in acidified water ecosystems. The toxic effect of Al has been attributed to inorganic Al (Ali), though there are few in situ studies in ambient humic waters which are the focus of this thesis.The aim was to estimate Ali toxicity and thus also Ali concentrations in Swedish humic streams. Subsequently it is necessary to analyse Ali correctly, which was studied by modelling and method intercalibrations. The hypothesis was that the effect of Ali could be followed via physiological effects and Al accumulation, as well as by mortality. Toxicity was studied by in stream exposures of brown trout (Salmo trutta L.) and two salmonid prey organisms (Gammarus pulex and Baetis rhodani) during spring flood.The modelling of the Ali fraction was performed using monitoring data covering all of Sweden with satisfactory results. The essential variables for Ali modelling were determined; Al, DOC, pH and F, while Fe, Ca and Mg had less effect. The automated analytical procedure for Ali (with cation exchange followed by complexation with pyrocatechol violet) was modified and validated and showed to be the preferred method for laboratory analyses.To avoid detrimental effects for brown trout Ali should be <20 µg/L and pH >5.0; mortality was high when the Ali was above 50 µg/L. The invertebrates were more sensitive, as mortalities occurred at pH <6.0 and Ali >15 µg/L for G. pulex, and at pH <5.7 and Ali >20 µg/L for B. rhodani. It is prudent to use a wide view and let the most sensitive species set the tolerance limits; a pH above 5.7-6.0 and Ali below 15-20 µg/L allows the stream ecosystems to thrive.Today, as waters are recovering from acidification, the aim of mitigating liming is to carefully adjust dosage to avoid suboptimal water quality. The thresholds found in this thesis can be used to efficiently but carefully decrease liming, as both Ali and pH levels have to be balanced to sustain the recovering aquatic biota.
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| 7. |
- Berglund, Sigrid, et al.
(author)
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Hydrogen production by a fully de novo enzyme
- 2024
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Other publication (other academic/artistic)abstract
- Molecular catalysts based on abundant elements that function in neutral water represent an essential component of sustainable hydrogen production. Artificial hydrogenases based on protein-inorganic hybrids have emerged as an intriguing class of catalysts for this purpose. We have prepared a novel artificial hydrogenase based on cobaloxime bound to a de novo three alpha-helical protein, α3C, via a pyridyl-based unnatural amino acid. The functionalized de novo protein was characterised by UV-visible, CD, and EPR spectroscopy, as well as MALDI spectrometry, which confirmed the presence and ligation of cobaloxime to the protein. The new de novo protein produced hydrogen under electrochemical, photochemical and reductive chemical conditions in neutral water solution. A change in hydrogen evolution capability of the de novo enzyme compared with native cobaloxime was observed, with turnover numbers around 80% of that of cobaloxime, and hydrogen evolution rates of 40% of that of cobaloxime. We discuss these findings in the context of existing literature, how our study contributes important information about the functionality of cobaloxime as hydrogen evolving catalysts in protein environments, and the feasibility of using de novo proteins for developent into artificial metalloenzymes. Small de novo proteins as enzyme scaffolds have the potential to function as upscalable bioinspired catalysts thanks to their efficient atom economy, and the findings presented here show that these types of novel enzymes are a possible product.
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| 8. |
- Eklund, Ann, et al.
(author)
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Believed effect - A prerequisite but not a guarantee for acceptance of carnivore management interventions
- 2020
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In: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 241
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Journal article (peer-reviewed)abstract
- Conflicts over wildlife and their potential impacts on human practices and livelihoods are widespread. Large carnivore predation on livestock often becomes a contested topic which has led to global declines in carnivore numbers over centuries. To minimise impacts of carnivores on human livelihoods and allow conservation, various interventions are used to prevent attacks. However, these interventions can only be effective if they are used and implemented. According to the Technology Acceptance Model, end user acceptance depends on perceived usefulness and ease of use. This study investigates the former as believed effect through a modified version of the Potential for Conflict Index. Using a web-based questionnaire we assess acceptance levels and believed effect of interventions intended to prevent carnivore predation on livestock, dogs, and reindeer among animal owners/keepers and members of the public in Sweden. The analysis shows that believed effect is a prerequisite for acceptance of an intervention, but not a guarantee. Interventions promoted by authorities are in some cases highly acceptable to users and the public, but in other cases believed contra-productive and are opposed by the end users. Active promotion of the latter may undermine mitigation efforts. Carnivore removal is generally more acceptable to animal owners than to members of the public. The results are useful to minimise conflicts within carnivore management and increase transparency and success of conservation. The results are discussed in relation to how similar questions may be approached in other systems using combined measures of believed effect, accept-intention, and the Potential for Conflict Index.
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| 9. |
- Eklund, Ann, et al.
(author)
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Drivers of intervention use to protect domestic animals from large carnivore attacks
- 2020
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In: Human Dimensions of Wildlife. - : Informa UK Limited. - 1087-1209 .- 1533-158X. ; 25:4, s. 339-354
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Journal article (peer-reviewed)abstract
- Large carnivores are prioritized in conservation, but their co-occurrence with humans and domestic animals can generate conflict. Interventions preventing carnivore attacks are central to carnivore conservation, but are only effective if implemented. This study investigates drivers of the intention to use interventions among animal owners in Sweden based on the Theory of Planned Behavior, extended with the emotion construct Worry. Additionally, the study includes an explorative analysis investigating the processes behind this worry based on the Appraisal Theory of Emotion. In a survey comprising 1,163 animal owners, the subjective norm is identified as an important driver in the regression model of intended intervention use. Adding Worry to the model increased the amount of explained variance. Worry, in turn was mainly explained by experienced vulnerability among animal owners. This study illustrates how emotion theory can extend TPB to enhance understanding of human behavior, important for future coexistence between humans and wildlife.
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| 10. |
- Eklöf, Hampus, et al.
(author)
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A prospective comparison of duplex ultrasonography, Captopril renography, MRA and CTA in assessing renal artery stenosis
- 2006
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In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 47:8, s. 764-774
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Journal article (peer-reviewed)abstract
- Purpose: To prospectively compare the diagnostic accuracy of duplex ultrasonography, captopril renography, computed tomography angiography (CTA), and 3D Gd magnetic resonance angiography (MRA) in diagnosing hemodynamically significant renal artery stenosis (RAS). Material and Methods: The standard of reference was measurement of transstenotic pressure gradient. Fifty-eight hypertensive patients with suspicion of RAS were evaluated, when possible, by all five techniques. Sensitivity and specificity to detect RAS were compared for each technique on both a patient and kidney basis. Discrepancies were evaluated separately and classified as borderline, method dependent, or operator dependent. Results: The prevalence of RAS was 77%. The sensitivity/specificity of ultrasonography, captopril renography, CTA, and MRA in detecting kidneys with RAS was 73/71%, 52/63%, 94/62%, and 93/91%, respectively. Ultrasonography had a significantly lower sensitivity than CTA and MRA (P < 0.001) but higher than captopril renography (P = 0.013). Borderline RAS was the main cause for discrepancies. Conclusion: MRA and CTA were significantly better than duplex ultrasonography and captopril renography in detecting hemodynamically significant RAS. The ultrasonography criteria for RAS based on the evaluation of renal peak systolic velocity and renal/aortic ratio are questionable. Captopril renography cannot be recommended for assessing RAS.
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| 11. |
- Erlandsson, Ann, 1968-, et al.
(author)
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High inducible nitric oxide synthase in prostate tumor epithelium is associated with lethal prostate cancer
- 2018
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In: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 52:2, s. 129-133
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to investigate the role of inducible nitric oxide synthase (iNOS) in lethal prostate cancer (PCa) by studying the iNOS immunoreactivity in tumor tissue from men diagnosed with localized PCa.MATERIALS AND METHODS: This study is nested within a cohort of men diagnosed with incidental PCa undergoing transurethral resection of the prostate (the Swedish Watchful Waiting Cohort). To investigate molecular determinants of lethal PCa, men who died from PCa (n = 132) were selected as cases; controls (n = 168) comprised men with PCa who survived for at least 10 years without dying from PCa during follow-up. The immunoreactivity of iNOS in prostate tumor epithelial cells and in cells of the surrounding stroma was scored as low/negative, moderate or high. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for lethal PCa according to iNOS category.RESULTS: There was no association between iNOS immunoreactivity in stroma and lethal disease. However, when comparing high versus low/negative iNOS immunoreactivity in epithelial cells, the OR for lethal PCa was 3.80 (95% CI 1.45-9.97).CONCLUSION: Patients with localized PCa have variable outcomes, especially those with moderately differentiated tumors. Identifying factors associated with long-term PCa outcomes can elucidate PCa tumor biology and identify new candidate prognostic markers. These findings support the hypothesis that high iNOS in tumor epithelium of the prostate is associated with lethal disease.
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| 12. |
- Erlandsson, Ann, 1968-, et al.
(author)
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Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy
- 2023
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In: International journal of immunopathology and pharmacology. - : Sage Publications. - 0394-6320 .- 2058-7384. ; 37
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Journal article (peer-reviewed)abstract
- Objectives: Androgen deprivation therapy (ADT) has long been a cornerstone in treatment of advanced prostate cancer (PCa), and is known to improve the results of radiotherapy (RT) for high-risk disease. The purpose of our study was to use a multiplexed immunohistochemical (mIHC) approach to investigate the infiltration of immune cells in PCa tissue after eight weeks of ADT and/or RT with 10 Gy.Methods: From a cohort of 48 patients divided into two treatment arms, we obtained biopsies before and after treatment and used a mIHC method with multispectral imaging to analyze the infiltration of immune cells in tumor stroma and tumor epithelium, focusing on areas with high infiltration.Results: Tumor stroma showed a significantly higher infiltration of immune cells compared to tumor epithelium. The most prominent immune cells were CD20(+) B-lymphocytes, followed by CD68(+) macrophages, CD8(+) cytotoxic T-cells, FOXP3(+) regulatory T-cells (Tregs), and T-bet(+) Th1-cells. Neoadjuvant ADT followed by RT significantly increased the infiltration of all five immune cells. Numbers of Th1-cells and Tregs significantly increased after single treatment with ADT or RT. In addition, ADT alone increased the number of cytotoxic T-cells and RT increased the number of B-cells.Conclusions: Neoadjuvant ADT in combination with RT results in a higher inflammatory response compared to RT or ADT alone. The mIHC method may be a useful tool for investigating infiltrating immune cells in PCa biopsies to understand how immunotherapeutic approaches can be combined with current PCa therapies.
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| 13. |
- Erlandsson, Ann, 1968-, et al.
(author)
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M2 macrophages and regulatory T cells in lethal prostate cancer.
- 2019
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In: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 79:4, s. 363-369
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tregs ) can contribute to cancer progression by suppressing the anti-tumor immune response. This study investigated the number of CD163-positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and Tregs .METHODS: This nested case-control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163-positive M2 macrophages and FOXP3/CD4-positive Tregs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and Tregs were assessed using Spearman's rank-order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts.RESULTS: The number of M2 macrophages and Tregs showed a significant correlation (P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23-3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis.CONCLUSIONS: Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as Tregs , promote an immunosuppressive environment.
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| 14. |
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| 15. |
- Orädd, Greger, et al.
(author)
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α-Methylene ordering of acyl chains differs in glucolipids and phosphatidylglycerol from Acholeplasma laidlawii membranes: 2H-NMR quadrupole splittings from individual lipids in mixed bilayers
- 2000
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In: Biochimica et Biophysica Acta (BBA) - Biomembranes. ; 1468:1-2, s. 329-44
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Journal article (peer-reviewed)abstract
- A Acholeplasma laidlawii strain A-EF22 was grown in a medium supplemented with α-deuterated oleic acid. Phosphatidylglycerol (PG), the glucolipids monoglucosyldiacylglycerol (MGlcDAG), diglucosyldiacylglycerol (DGlcDAG) and monoacyldiglucosyldiacylglycerol, and the phosphoglucolipid glycerophosphoryldiglucosyldiacylglycerol (GPDGlcDAG) were purified, and the phase behaviour and molecular ordering for the individual lipids, as well as for mixtures of the lipids, were studied by 2H-, 31P-NMR and X-ray scattering methods. The chemical structure of all the A. laidlawii lipids, except PG, has been determined and verified previously; here also the chemical structure of PG was verified, utilising mass spectrometry and 1H and 13C high resolution NMR spectroscopy. For the first time, lipid dimers were found in the mass spectrometry measurements. The major findings in this work are: (1) addition of 50 mol% of PG to the non-lamellar-forming lipid MGlcDAG does not significantly alter the transition temperature between lamellar and non-lamellar phases; (2) the 2H-NMR quadrupole splitting patterns obtained from the lamellar liquid crystalline phase are markedly different for PG on one hand, and DGlcDAG and GPDGlcDAG on the other hand; and (3) mixtures of PG and DGlcDAG or MGlcDAG give rise to 2H-NMR spectra consisting of a superposition of splitting patterns of the individual lipids. These remarkable features show that the local ordering of the α-carbon of the acyl chains is different for PG than for MGlcDAG and DGlcDAG, and that this difference is preserved when PG is mixed with the glucolipids. The results obtained are interpreted in terms of differences in molecular shape and hydrophilicity of the different polar headgroups.
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| 16. |
- Rider, Jennifer R., et al.
(author)
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iNOS expression and lethal prostate cancer in patients with localized disease
- 2017
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In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; :22S
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Journal article (peer-reviewed)abstract
- Inducible nitric oxide synthase (iNOS) has demonstrated both tumor-promoting and tumor-inhibiting effects in prostate cancer. However, the relationship between iNOS protein expression and long-term prostate cancer outcomes is unclear. We evaluated iNOS expression in tumor epithelia and stroma in 300 men with localized tumors diagnosed incidentally by transurethral resection of the prostate (TURP) in Sweden. In this extreme case-control design, cases (N=132) died of prostate cancer and controls (N=168) survived at least 8 years following diagnosis without death from prostate cancer or a competing cause. Immunohistochemistry was undertaken with a polyclonal rabbit anti-human NOS2 antibody (Abcam) and the Ventana (Roche) semi-automated staining system. Two observers individually scored the staining according to intensity and number of positive cells from 0-3. The median value across cores in each patient were then categorized as <1, >1-<2, and >2, separately for epithelial and stromal compartments. Odds ratios for lethal prostate cancer were estimated with logistic regression controlling for the matching factors (age, calendar year of diagnosis), as well as tumor stage, Gleason score, and percent tumor. iNOS was expressed by stromal-associated M1 macrophages and fibroblasts, as well as tumor cells. Gleason score was positively associated with both stromal and epithelial iNOS staining. In the stroma, there was no statistically significant association between iNOS expression and lethal prostate cancer after adjustment for clinical covariates. However, the odds of lethal prostate cancer increased with tumor expression of iNOS in the fully adjusted model. Compared to patients with the lowest category of iNOS expression, the odds ratios for lethal prostate cancer were 2.96 (95% CI: 1.26-6.96) for patients in the second category and 3.80 (95% CI: 1.45-9.97) for patients in the top category. These results suggest that iNOS may help to identify patients with aggressive prostate cancer at the time of diagnosis, or may be a therapeutic target. Given previously reported in vitro data suggesting that iNOS promotes proliferation of androgen-independent prostate tumors, future analyses will investigate association between iNOS expression and time to castration-resistant prostate cancer in this patient population.
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| 17. |
- Tegelberg, Åke, et al.
(author)
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Bed partners' and patients' experiences after treatment of obstructive sleep apnoea with an oral appliance
- 2012
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In: Swedish Dental Journal. - : Sveriges tandläkarförbund. - 0347-9994. ; 36:1, s. 35-44
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Journal article (peer-reviewed)abstract
- The purpose of the study was to evaluate bed-partners' and patients' self-reports of general well-being, physical strength and mental energy after treatment for obstructive sleep apnoea (OSA) with a mandibular advancement oral appliance (OA). Patients (N = 134) referred from medical physicians diagnosed with true OSA, i.e. an apnoea-hypopnoea index of > 10, were treated with an OA for more than one year. The somnographic evaluations were undertaken in a patient's home before the start of, and six months after, treatment. An individually designed monobloc OA was manufactured by a dental technician for nightly use. After one year of treatment, a follow-up questionnaire was sent to patients whose sleep disorder was reduced > 50% from baseline values and to their bed partners. The questionnaire consisted of 15 questions or statements with multi-answer alternatives concerning well-being, physical strength, mental energy, sleep, day and night symptoms, and the Epworth Sleepiness Scale (ESS: eight questions). The questionnaire was answered by 82% (110/134) of the patients and 85 bed partners. Both patients and bed partners reported improvement in general well-being, physical strength and mental energy, between 70-80% for patients and 55-68% for bed partners sharing the same bed-room. Similar results were found for concentration ability, joyfulness and strength of effort in social intercourse, as well as decreased daytime sleepiness, improvement in the feeling of getting enough sleep and reduced nocturia. Conclusions: In all dimensions, the treatment effect had a great influence, not only on patients but on bed partners as well.
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| 18. |
- Wohlin, Martin, et al.
(author)
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Apolipoprotein E epsilon 4 genotype is independently associated with increased intima-media thickness in a recessive pattern
- 2007
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In: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 42:5, s. 451-456
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Journal article (peer-reviewed)abstract
- Polymorphisms in the apolipoprotein E (Apo E) gene have been associated with lipid levels, carotid intima media thickness (CCA-IMT), inflammation and cardiovascular disease (CVD). Earlier findings suggested an association of the Apo E alleles with increased CCA-IMT following a recessive pattern. Whether associations might be independent of C-reactive protein (CRP), lipid levels and other CVD risk factors is not known. We investigated the relationships between Apo E (epsilon2, epsilon3 and epsilon4 alleles) and CCA-IMT, measured by B-mode ultrasound, in dominant and recessive models in a community-based sample of 437 men 75 years of age. In men homozygous for the epsilon4 allele CCA-IMT was significantly increased by 0.13 mm to 0.86 +/- 0.16 mm compared to 0.73 +/- 0.19 mm in non- epsilon4-carriers (P = 0.0012) and 0.73 +/- 0.21 mm in epsilon4 heterozygous (P = 0.0044) in unadjusted recessive models. The association between Apo E epsilon4 genotype and CCA-IMT was independent of Apo E epsilon2 and Apo E epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes) (P = 0.018). No relations between Apo E genotype and CCA-IMT were observed in dominant models. No significant associations between the Apo E epsilon2 and epsilon3 alleles and CCA-IMT were found. In this study, men homozygous with the ApoE epsilon4 allele had thicker CCA-IMT, independently of Apo E epsilon2 and epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes), suggesting CCA-IMT to be modified by the ApoE epsilon4 genotype in a recessive pattern.
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