| 1. |
- Bengtsson Boström, Kristina, et al.
(author)
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Interaction between the angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea as a mechanism for hypertension
- 2007
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In: J Hypertens. - 0263-6352. ; 25:4, s. 779-783
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Obstructive sleep apnoea (OSA) confers a risk of hypertension and cardiovascular complications. Both the renin-angiotensin-aldosterone system and OSA are important determinants of blood pressure, but it is not fully known how they interact. The aim of this study was to explore the interaction between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and OSA in the association with hypertension. DESIGN: A community-based, case-control design with hypertensive patients in primary care (n = 157) and normotensive population controls (n = 181). METHODS: All subjects underwent ambulatory polysomnography during one night. OSA was defined by a minimum of 10 apnoea/hypopnoea events per hour. Office blood pressure was measured and hypertension status was assessed. The genotypes were determined using polymerase chain reaction. RESULTS: An interaction analysis including sex, ACE I/D polymorphism (DD and ID versus II), and OSA identified a significant interaction between OSA and the ACE I/D polymorphism: odds ratio (OR) 6.3, 95% confidence interval (CI) 1.8-22.5, P = 0.004 as well as between OSA and sex: OR 3.3, 95% CI 1.1-9.6, P = 0.033. OSA was significantly associated with hypertension in men but not in women. CONCLUSION: The interaction between the ACE gene I/D polymorphism and OSA appears to be an important mechanism in the development of hypertension, particularly in men.
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| 2. |
- Buschard, Karsten, et al.
(author)
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Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project
- 2005
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 22:9, s. 1190-8
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Journal article (peer-reviewed)abstract
- AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
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| 3. |
- Hedner, Jan A, 1953, et al.
(author)
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Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study
- 2006
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 27:3, s. 564-70.
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Journal article (peer-reviewed)abstract
- Obstructive sleep apnoea (OSA) is a recognised risk factor for hypertension (HT). The current authors investigated confounders of this association in a sex-balanced community-based sample of patients with HT (n=161) from the Skaraborg Hypertension and Diabetes Project (n=1,149) and normotensive controls (n=183) from an age and sex stratified community-based population sample (n=1,109). All participants underwent ambulatory home polysomnography. Severe OSA (apnoea-plus-hypopnoea index (AHI) >= 30 events center dot h(-1)) was found in 47 and 25% of hypertensive and normotensive males, respectively. The corresponding numbers in females were 26 and 24%, respectively. The odds ratio (OR) for HT increased across AHI tertiles from 1.0 to 2.1 (95% confidence interval: 0.9-4.5) and 1.0 to 3.7 (95% CI: 1.7-8.2) in males, but not in females where the OR increased from 1.0 to 1.8 (95% CI: 0.8-3.9) and 1.0 to 1.6 (95% CI: 0.7-3.5). Regression analysis correcting for age, body mass index (or waist-hip ratio) and smoking did not eliminate the association between OSA and HT in males. The present data suggest that obstructive sleep apnoea is highly prevalent in both the general population and in patients with known hypertension. The contribution of obstructive sleep apnoea to hypertension risk may be sex dependent and higher in males than in females.
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| 4. |
- Ingelsson, Erik, et al.
(author)
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The PPARGC1A Gly482Ser polymorphism is associated with left ventricular diastolic dysfunction in men.
- 2008
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In: BMC cardiovascular disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 8
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Gly482Ser polymorphism in peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) has been demonstrated to be associated with diabetes, obesity and hypertension, all of which are important risk factors for left ventricular diastolic dysfunction. METHODS: The PPARGC1A Gly482Ser polymorphism was genotyped in a community-based cohort of 499 men and 533 women, who also underwent an echocardiographic examination to determine their left ventricular diastolic function. The association between the polymorphism and the presence of diastolic dysfunction was evaluated using logistic regression models. RESULTS: The Ser allele of the PPARGC1A Gly482Ser polymorphism was significantly associated with a lower risk of diastolic dysfunction in men, but not in women. In a model adjusting for potential confounders (age, body mass index, leisure time physical activity, hypertension and diabetes) the results were still significant and substantial (odds ratio 0.13, 95% confidence interval 0.03-0.54, p for trend = 0.004). The results were consistent in a series of models, and they imply a multiplicative, protective effect of the Ser allele, with lower risk of diastolic dysfunction for each copy of the allele. CONCLUSION: The Ser allele of the PPARGC1A Gly482Ser polymorphism was associated with decreased risk of diastolic left ventricular dysfunction in men, but not in women, in our large community-based sample. It was associated with a substantially decreased risk, even after adjustment for potential confounders. The clinical importance of the findings has to be established in further studies.
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| 5. |
- Johansson, Magnus C, 1954, et al.
(author)
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The influence of patent foramen ovale on oxygen desaturation in obstructive sleep apnoea
- 2007
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 0903-1936 .- 1399-3003. ; 29:1, s. 149-55
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Journal article (peer-reviewed)abstract
- Obstructive sleep apnoea (OSA) is associated with oxygen desaturation to a varying degree. A patent foramen ovale (PFO) may allow interatrial right-to-left shunting. The hypothesis of the current study was that oxygen desaturation will occur more often, in proportion to the frequency of respiratory disturbances, in OSA subjects with PFO than in those without. In a group of 209 subjects diagnosed with OSA, the proportion of desaturation to respiratory events was calculated as the ratio of oxygen desaturation index (ODI)/apnoea-hypopnoea index (AHI). A total of 15 cases with high proportional desaturation (ODI/AHI >or=0.66) were individually matched with 15 controls with low proportional desaturation (ODI/AHI or=20 bubbles passed over from the right to the left atrium after a single injection. The prevalence of large PFO was nine out of 15 (60%) in the high proportional desaturation group versus two out of 15 (13%) in the low proportional desaturation group. The median number of passing bubbles was positively correlated to minimum oxygen saturation among those with PFO. In conclusion, oxygen desaturation occurs more often, in proportion to the frequency of respiratory disturbances, in obstructive sleep apnoea subjects with a patent foramen ovale than in those without.
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| 6. |
- Moen, Janne, et al.
(author)
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Factors associated with multiple medication use in different age groups
- 2009
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In: The Annals of Pharmacotherapy. - 1060-0280 .- 1542-6270. ; 43:12, s. 1978-1985
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Journal article (peer-reviewed)abstract
- BACKGROUND: Multiple medicine use among elderly persons is likely to be the result of treatment regimens developed over a long period of time. By learning more about how multiple medication use develops, the quality of prescribing may be improved across the adult lifespan. OBJECTIVE: To describe patterns of multiple medicine use in the general Swedish population and its association with sociodemographic, lifestyle, and health status factors. METHODS: Data from a cross-sectional population health survey collected during 2001-2005 from 2816 randomly selected Swedish residents (age 30-75 y; response rate 76%) were analyzed. Multiple medicine use was restricted to prescription drugs and defined as the 75th percentile; that is, the 25% of the study group using the highest number of drugs per individual. RESULTS: Seventy-one percent of the respondents used some kind of drug, 51.5% used one or more prescription drug, 38.4% used one or more over-the-counter (OTC) medication, and 8.3% used one or more herbal preparation. The cutoff amounts defining multiple medicine use were: 2 or more medications for 30- to 49-year-olds, 3 or more for 50- to 64-year-olds, and 5 or more for 65- to 75-year-olds. No association between use of multiple medicines and use of OTC drugs or herbal preparations was found. When drugs were classified into therapeutic subgroups, 76.3% of those aged 30-49 years, 97.9% of those aged 50-64 years, and 100% of those aged 65-75 years were taking a unique combination of drugs. Multivariate analyses showed that diabetes and poor self-rated health were associated with multiple medicine use in all age cohorts. Female sex and hypertension were associated with multiple medicine use among those aged 30-49 and 50-64 years, current smoking among those aged 50-64 years, and obesity among those aged 65-75 years. CONCLUSIONS: Multiple medicine use was associated with morbidity and poor self-rated health across all age groups. The vast majority of users of multiple drugs are taking a unique combination of medications.
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| 7. |
- Nilsson, Sven E., et al.
(author)
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Low systolic blood pressure is associated with impaired cognitive function in the oldest old: longitudinal observations in a population-based sample 80 years and older
- 2007
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In: Aging clinical and experimental research. - 1720-8319. ; 19:1, s. 41-47
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Journal article (peer-reviewed)abstract
- Background and aims: The primary aim of the present study was to examine whether there is an association between blood pressure and the risk of subsequent cognitive decline in the oldest old. Various factors associated with blood pressure and cognitive function were considered. Methods: The study comprised 599 individuals of a population-based sample, 199 men (mean age at baseline 82.8 years, range 80-95) and 400 women (mean age at baseline 83.3 years, range 80-100). Cognitive function was evaluated by the Mini Mental State Examination (MMSE). For a subgroup of 385 subjects (130 men, 255 women), data were available on blood pressure and MMSE at baseline and two follow-ups at two-year intervals. Baseline blood pressure was studied in one group with reduced cognition and in another group with intact cognition across the following four years. The association of systolic blood pressure (SBP) with the MMSE score through the follow-up period was analysed controlling for frailty (time to death), age, gender, apoprotein E, homocysteine, hypertension, congestive heart failure, and stroke. Results: A medical history of arterial hypertension was associated with lower MMSE scores and a higher prevalence of dementia and cognitive decline at baseline. However, intact cognition through the observation period was associated with higher baseline SBP. This relationship also remained when the frailty of aging subjects, indicated by remaining time to death, was taken into account. Conclusions: Lower SBP in the oldest old is associated with an increased risk of cognitive impairment even after adjustment for compromised vitality. In late life, the risk of cognitive decline needs to be considered in clinical practice.
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| 8. |
- Nyholm, Maria, et al.
(author)
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The validity of obesity based on self-reported weight and height: Implications for population studies
- 2007
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In: Obesity. - Hoboken : Wiley. ; 15:1, s. 197-208
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To validate self-reported information on weight and height in an adult population and to find a useful algorithm to assess the prevalence of obesity based on self-reported information. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional survey consisting of 1703 participants (860 men and 843 women, 30 to 75 years old) conducted in the community of Vara, Sweden, from 2001 to 2003. Self-reported weight, height, and corresponding BMI were compared with measured data. Obesity was defined as measured BMI > or = 30 kg/m2. Information on education, self-rated health, smoking habits, and physical activity during leisure time was collected by a self-administered questionnaire. RESULTS: Mean differences between measured and self-reported weight were 1.6 kg (95% confidence interval, 1.4; 1.8) in men and 1.8 kg (1.6; 2.0) in women (measured higher), whereas corresponding differences in height were -0.3 cm (-0.5; -0.2) in men and -0.4 cm (-0.5; -0.2) in women (measured lower). Age and body size were important factors for misreporting height, weight, and BMI in both men and women. Obesity (measured) was found in 156 men (19%) and 184 women (25%) and with self-reported data in 114 men (14%) and 153 women (20%). For self-reported data, the sensitivity of obesity was 70% in men and 82% in women, and when adjusted for corrected self-reported data and age, it increased to 81% and 90%, whereas the specificity decreased from 99% in both sexes to 97% in men and 98% in women. DISCUSSION: The prevalence of obesity based on self-reported BMI can be estimated more accurately when using an algorithm adjusted for variables that are predictive for misreporting.
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| 9. |
- Odeberg, Jacob, et al.
(author)
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The Asp298 allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus.
- 2008
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In: BMC cardiovascular disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Endothelial dysfunction plays a central role in atherosclerotic progression and cardiovascular complications of type 2 diabetes mellitus (T2DM). Given the role of nitric oxide in the vascular system, we aimed to test hypotheses of synergy between the common endothelial nitric oxide synthase (eNOS) Asp298 allele and T2DM in predisposing to acute myocardial infarction (AMI). METHODS: In a population-based patient survey with 403 persons with T2DM and 799 healthy subjects from the population without diabetes or hypertension, we analysed the relation between T2DM, sex and the eNOS Asp298 allele versus the risk for AMI. RESULTS: In an overall analysis, T2DM was a significant independent risk factor for AMI. In patients with T2DM, homozygosity for the eNOS Asp298 allele was a significant risk factor (HR 3.12 [1.49-6.56], p = 0.003), but not in subjects without diabetes or hypertension. Compared to wild-type non-diabetic subjects, all patients with T2DM had a significantly increased risk of AMI regardless of genotype. This risk was however markedly higher in patients with T2DM homozygous for the Asp298 allele (HR 7.20 [3.01-17.20], p < 0.001), independent of sex, BMI, systolic blood pressure, serum triglycerides, HDL -cholesterol, current smoking, and leisure time physical activity. The pattern seemed stronger in women than in men. CONCLUSION: We show here a strong independent association between eNOS genotype and AMI in patients with T2DM. This suggests a synergistic effect of the eNOS Asp298 allele and diabetes, and confirms the role of eNOS as an important pathological bottleneck for cardiovascular disease in patients with T2DM.
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| 10. |
- Prokopenko, Inga, et al.
(author)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
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Journal article (peer-reviewed)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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