IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients.

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

Cost analysis of different pharmacological treatment strategies in elderly hypertensives.

OBJECTIVE: To compare costs for management of hypertension in elderly hypertensives randomized to starting treatment with conventional (beta-blockers/diuretics) therapy or a therapy initiated with a calcium antagonist or an angiotensin-converting enzyme (ACE) inhibitor. DESIGN: Health economic substudy in the Swedish Trial in Old Patients with Hypertension-2 (STOP Hypertension-2). SETTING: Outpatient clinics in Sweden. In this health economics substudy, 16/312 participating STOP-2 trial centers were selected. SUBJECTS: Elderly (70--84 years) patients (n=303) with a systolic and/or diastolic hypertension (or=180 and/or 105 mmHg). METHODS: Costs for patient management were analyzed and categorized in costs for routine care (protocol-driven costs, PDC), costs for extra visits or care (non-protocol-driven costs, NPDC), and direct drug costs (drug treatment costs, DTC). All calculations are related to costs during the first year of treatment after inclusion in STOP Hypertension-2. RESULTS: Out of the scheduled visits, a total of 99% were actually performed by the patients. There were no differences in the number of visits between the three treatment groups (diuretics/beta-blockers, calcium antagonists or ACE inhibitors). PDC did thus not differ between the three treatment groups. NPDC were similar in the conventional and calcium antagonist groups and lower than for the ACE inhibitor group. DTC were lower in the conventional treatment group compared with the other two groups. CONCLUSION. In elderly hypertensives in STOP Hypertension-2, total costs for management of hypertension were lower in patients assigned to diuretics, beta-blockers or calcium antagonists compared with ACE inhibitors during the first year of treatment. These results may be relevant to management of elderly hypertensive patients, especially in those patients without compelling indications or contraindications to starting treatment with either of these three main drug alternatives. Notably, with a specific drug regimen there are sizable NPDC such as extra visits and controls associated with symptoms or side-effects of a specific therapy, which significantly add to the total costs of treatment. Such costs, beyond the actual costs for the drugs, are important to realize and evaluate in order to provide the true costs for treatment of hypertensive patients.

Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-Hypertension-2.

OBJECTIVE: To perform a subgroup analysis on those patients in STOP-Hypertension-2 who had isolated systolic hypertension. DESIGN AND METHODS: The STOP-Hypertension-2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs (diuretics, beta-blockers) with that of newer ones [angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists]. In all, 6614 elderly patients with hypertension (mean age 76.0 years, range 70-84 years at baseline) were included in STOP-Hypertension-2. In the present subgroup analysis of STOP-Hypertension-2, isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg, in accordance with the Syst-Eur and Syst-China study criteria. In total, 2280 patients in STOP-Hypertension-2 met these criteria. In the study, patients were randomized to one of three treatment groups: "conventional" antihypertensive therapy with beta-blockers or diuretics (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily); ACE inhibitors (enalapril 10 mg or lisinopril 10 mg daily); or calcium antagonists (felodipine 2.5 mg or isradipine 2.5 mg daily). Analysis was by intention to treat. RESULTS: The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens: 35/13 mmHg in the conventional group (n=717), 34/12 mmHg in the ACE inhibitor group (n = 724), and 35/13 mmHg in the calcium antagonist group (n=708). Prevention of cardiovascular mortality, the primary endpoint of the study, did not differ between the three treatment groups. All stroke events, i.e. fatal and non-fatal stroke together, were significantly reduced by 25% in the newer-drugs group compared with the conventional group (95% CI 0.58-0.97; p=0.027). This difference was attributable to reduction of non-fatal stroke while fatal stroke events did not differ between groups. New cases of atrial fibrillation were significantly increased by 43% (95% CI 1.02-1.99; p=0.037) on "newer" drugs compared with "conventional" therapy, mainly attributable to the calcium antagonists. There were no significant differences between the three treatment groups with respect to the risks of myocardial infarction, sudden death or congestive heart failure. CONCLUSIONS: The analysis demonstrated that "newer" therapy (ACE inhibitors/calcium antagonists) was significantly better (25%) than "conventional" (diuretics/beta-blockers) in preventing all stroke in elderly patients with isolated systolic hypertension.

Serum lipids and lipoproteins in relation to endogenous and exogenous female sex steroids and age. The Women's Health in the Lund Area (WHILA) study.

BACKGROUND: Different studies have presented conflicting results concerning the effect of menopause on lipid levels. AIMS: To describe the serum lipid profile and the prevalence of hyperlipidemia in women aged 50-60 and the perceived relation to endogenous and exogenous hormones and age. METHODS: Out of a total population of 10,766 women aged 50-59 years, 6908 (64%) participated in a health assessment program, including a lipid profile evaluation. The women were grouped according to hormonal status into pre-menopausal (PM), post-menopausal without hormone replacement therapy (PM0) (HRT) and post-menopausal with hormone replacement therapy (PMT). Age groups used were 50-54, 55-59 and >60 years. RESULTS: Serum cholesterol and triglycerides increased significantly by age in PM0 (P < 0.0001) and triglycerides also in PMT (P < 0.0001). Serum high-density lipoprotein cholesterol (HDL) levels decreased significantly by age in PMT (P = 0.002) and low-density lipoprotein cholesterol (LDL) increased in PM0 (P < 0.0001) and PMT (P = 0.007). The co-prevalence of levels of cholesterol >7 and triglycerides >2 mmol/l decreased by age in PM, but increased by age in PM0 and PMT. The prevalence of high-risk lipid levels and the prevalence of coexisting additional two metabolic risk factors were higher in the PM0 compared to the PMT group. The prevalence of serum triglycerides >1.5 and serum cholesterol >5 mmol/l were increasing by age in each of the hormonal groups. CONCLUSIONS: These data suggest that loss of endogenous sex steroids contribute substantially to an increased atherogenic lipid profile. Hormone replacement therapy may partly reverse these differences.

Biological factors are more important than socio-demographic and psychosocial conditions in relation to hypertension in middle-aged women. The Women's Health in the Lund Area (WHILA) study.

The objective of this cross-sectional study was to analyse the influence of biological, socio-demographic, and psychosocial factors and current perimenopausal status on hypertension in a geographically defined population of 10,766 women aged 50-59 years, of whom 6901 attended the study. Altogether 1887 (27.3%) women had hypertension: 996 with drug treatment and 891 diagnosed at the study. In a logistic multiple regression analysis (controlled for age), drug treatment of hyperlipidaemia, family history of hypertension, waist-to-hip ratio, body mass index (BMI) increase > or = 25% during the past 25 years, S-triglycerides, S-cholesterol, education up to comprehensive school, and to upper secondary school, consumption of 84-167 g of alcohol/week, and of > or = 168 g of alcohol/week, were positively associated with hypertension, while high-density lipoprotein cholesterol and current smoking were negatively associated. A significant interaction was found between current smoking and BMI increase, with a lower risk for hypertension among smokers who had increased their BMI > or = 25%. No interaction was found between smoking and alcohol. In conclusion, hypertension was predominantly associated with biological factors, and with heredity for hypertension. Of the socio-demographic factors, only low level of education was associated with hypertension in a comprehensive analysis. Perimenopausal status showed no relation to occurrence of hypertension in the multiple regression analysis. The risk for hypertension increased with moderate and high consumption of alcohol, whereas smoking showed a decreased risk. Among women with weight gain, present smoking remained protective. Although both smoking and hypertension are established risk factors for cardiovascular disease, they seem not to be directly linked, indicating a complexity of mechanisms.

[High sense of coherence can have health enhancing effects]. / Hög känsla av sammanhang kan ha hälsofrämjande effekter.

Sense of coherence (SOC), e.g. meaningfulness of life, is according to the sociologist A. Antonovsky a health-promoting construct, which has been used in a number of descriptive studies in various populations. The aim of this population-based cross-sectional study was to investigate if middle-aged women with a self-reported low level of SOC also differed in biological variables, e.g. related to glucose and lipid metabolism, from women with a high level of SOC. These variables could potentially represent links in the pathophysiological chain of events causing somatic disease. We found significant differences according to dyslipidaemia (low HDL cholesterol and increased triglyceride levels) between groups of women with differing SOC scores, most negative findings were found in the group with lowest SOC. Women with medium-high or high SOC also reported less symptoms and need of regular medical controls. The results support a potential association between cognitive processes (SOC) and biological mechanisms causing adverse health effects.

The influence of hormonal status and features of the metabolic syndrome on bone density: a population-based study of Swedish women aged 50 to 59 years. The women's health in the Lund area study.

This study investigated whether there is an association between bone density and features of the metabolic syndrome in relation to hormonal status. All women aged 50 to 59 years living in a defined geographic area in Sweden were offered a health assessment program including blood glucose, lipid profile, blood pressure, and bone densitometry. Women were divided into 3 groups according to their hormonal status: premenopausal (PM), postmenopausal with hormone replacement therapy (PMT), and postmenopausal without hormone replacement therapy (PM0). Of the 6,886 women investigated, 7% were PM, 41% PMT, and 52% PM0. The overall prevalence of osteopenia and osteoporosis, according to the World Health Organization (WHO) definition, was 42.6% and 6.6%, respectively. T-score in the PM group was higher than in the PMT (P <.05) and PM0 groups (P <.001) and higher in the PMT group compared with the PM0 group (P <.001). Also, in the total cohort, the bone density was positively associated with body weight, body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum triglycerides, and blood glucose (P <.001 for all) and negatively associated with serum levels of cholesterol (P <.05) and high-density lipoprotein (HDL) (P <.001). This was most evident among the PMO women, suggesting that the influence of metabolic factors on bone density increases when the levels of hormones decrease. This indicates that hormone replacement therapy maintains treated women in a premenopausal status concerning the metabolic factors.