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1.  The association between self-rated health and impaired glucose tolerance in Swedish adults: A cross-sectional study 
Abstract
Objective
To investigate gender differences in the association between self-rated health (SRH) and impaired glucose tolerance (IGT) in subjects unaware of their glucose tolerance.
Design
A cross-sectional population-based study.
Setting
The two municipalities of Vara and Skövde in south-western Sweden.
Subjects
A total of 2502 participants (1301 women and 1201 men), aged 30–75, were randomly selected from the population.
Main outcome measures
IGT was regarded as the outcome measure and SRH as the main risk factor.
Results
The prevalence of IGT was significantly higher in women (11.9%) than in men (10.1%), (p = 0.029), as was the prevalence of low SRH (women: 35.4%; men: 22.1%, p = 0.006). Both men and women with low SRH had a poorer risk factor profile than those with high SRH, and a statistically significant crude association between SRH and IGT was found in both men (OR = 2.8, 95% CI 1.8–4.4) and women (OR = 1.5, 95% CI 1.0–2.2, p = 0.033). However, after controlling for several lifestyle factors and biomedical variables, the association was attenuated and remained statistically significant solely in men (OR = 2.3, 95% CI 1.2–4.3).
Conclusion
The gender-specific associations found between SRH and IGT suggest that SRH may be a better indicator of IGT in men than in women. Future studies should evaluate the utility of SRH in comparison with objective health measures as a potential aid to health practitioners when deciding whether to screen for IGT and T2DM.
doi:10.3109/02813432.2013.784541
PMCID: PMC3656394  PMID: 23621319
Gender; general practice; impaired glucose tolerance; self-rated health; Sweden
2.  Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population 
Background
The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population.
Methods
The study is based on a random sample of a Swedish population of men and women aged 30–74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7.
Results
In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: β=−0.143 p<0.001) and systolic blood pressure (systolic blood pressure β=−0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: β=−0.113 p<0.001; systolic blood pressure β=−0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=−0.024 p<0.001) and women (B=−0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=−0.014, p=0.008).
Conclusion
In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure.
doi:10.1186/1471-2261-13-30
PMCID: PMC3663757  PMID: 23594436
Sex hormone binding globulin (SHBG); Testosterone; Gender; Hypertension; BMI
3.  Inverse association between serum insulin and sex hormone-binding globulin in a population survey in Sweden 
Endocrine Connections  2012;2(1):18-22.
Objectives
Obesity is associated with low levels of sex hormone-binding globulin (SHBG). While the reason is not fully understood, we aimed to study the association between serum insulin and levels of SHBG in a random population.
Design and methods
Between 2001 and 2005, a random sample of 2816 participants aged 30–74 years were enrolled in a cross-sectional survey in the South-west of Sweden. Fasting blood samples were collected and an oral glucose tolerance test (OGTT) was conducted in all subjects without known diabetes. Diabetes mellitus was defined according to criteria from WHO, and clinical characteristics were used to discriminate between type 1 (T1D) and type 2 diabetes (T2D). Analyses of SHBG were successful in 2782 participants (98%), who thus constituted the current study population.
Results
We found significant inverse association between levels of SHBG and fasting serum insulin in both genders (men: β=−0.090, P=0.001; women: β=−0.197, P<0.001), which was independent of differences in age and BMI. The associations remained when also differences in fasting plasma glucose were accounted for (men: β=−0.062, P=0.022; women: β=−0.176, P≤0.001). Subjects with T1D exhibited higher levels of SHBG than both T2D (men: δ=15.9 nmol/l, P<0.001; women: δ=71.1 nmol/l, P<0.001) and non-diabetic subjects (men: δ=15.1 nmol/l, P<0.001; women: δ=72.9 nmol/l, P<0.001) independent of age, BMI and fasting glucose levels.
Conclusion
These findings are consistent with high levels of SHBG in T1D, and correspondingly low levels in T2D subjects, suggesting an inhibitory effect of insulin on the SHBG production in the liver.
doi:10.1530/EC-12-0057
PMCID: PMC3680959  PMID: 23781314
sex hormone-binding globulin; insulin; liver; diabetes
4.  Blood Pressure and Global Risk Assessment in a Swedish Population 
This study investigated the association between SCORE and the 2007 ESH-ESC blood pressure categories and explored achievements of blood pressure goals considering global risk. In 2001–2005, a random sample of inhabitants aged 30–74 years in southwestern Sweden was invited to a survey of cardiovascular risk factors. The study enrolled 2816 participants (participation rate 76%). Blood pressure was categorized according to the 2007 ESH-ESC guidelines. Global risk of 10-year CVD death was estimated using the Swedish SCORE chart also accounting for additional risk from diabetes (SCORE-DM). SCORE-DM increased in both sexes from optimal blood pressure to manifest hypertension but did not differ between the normal blood pressure categories. However, SCORE-DM became significantly higher among those with temporarily high blood pressure (men 3.3 SD (1.7), women 1.1 (1.8)) and hypertension (3.6 (2.0), 2.0 (2.0)), compared to optimal blood pressure (1.6 (2.9), 0.6 (1.9)). In the presence of both hypertension and diabetes, high-risk subjects dominated (men 76%, women 61%), and correspondingly a major proportion of patients with known hypertension were at high risk at a blood pressure ≥160/100 mm Hg. These findings have strong implications on blood pressure evaluation in clinical practice and support the use of SCORE to evaluate global risk.
doi:10.1155/2012/835812
PMCID: PMC3443609  PMID: 22991653
5.  Marked Genomic Diversity of Norovirus Genogroup I Strains in a Waterborne Outbreak 
Marked norovirus (NoV) diversity was detected in patient samples from a large community outbreak of gastroenteritis with waterborne epidemiology affecting approximately 2,400 people. NoV was detected in 33 of 50 patient samples examined by group-specific real-time reverse transcription-PCR. NoV genotype I (GI) strains predominated in 31 patients, with mixed GI infections occurring in 5 of these patients. Sequence analysis of RNA-dependent polymerase-N/S capsid-coding regions (∼900 nucleotides in length) confirmed the dominance of the GI strains (n = 36). Strains of NoV GI.4 (n = 21) and GI.7 (n = 9) were identified, but six strains required full capsid amino acid analyses (530 to 550 amino acids) based on control sequencing of cloned amplicons before the virus genotype could be determined. Three strains were assigned to a new NoV GI genotype, proposed as GI.9, based on capsid amino acid analyses showing 26% dissimilarity from the established genotypes GI.1 to GI.8. Three other strains grouped in a sub-branch of GI.3 with 13 to 15% amino acid dissimilarity to GI.3 GenBank reference strains. Phylogenetic analysis (2.1 kb) of 10 representative strains confirmed these genotype clusters. Strains of NoV GII.4 (n = 1), NoV GII.6 (n = 2), sapovirus GII.2 (n = 1), rotavirus (n = 3), adenovirus (n = 1), and Campylobacter spp. (n = 2) were detected as single infections or as mixtures with NoV GI. Marked NoV GI diversity detected in patients was consistent with epidemiologic evidence of waterborne NoV infections, suggesting human fecal contamination of the water supply. Recognition of NoV diversity in a cluster of patients provided a useful warning marker of waterborne contamination in the Lilla Edet outbreak.
doi:10.1128/AEM.07350-11
PMCID: PMC3298152  PMID: 22247153
6.  Prevalence, awareness, treatment, and control of hypertension: Rule of thirds in the Skaraborg project 
Objective
To describe the prevalence, awareness, and control of hypertension in a Swedish population during the early 2000s to address implications for care and prevention.
Design
A cross-sectional population survey.
Setting
Primary health care in Skaraborg, a rural part of western Sweden.
Subjects
Participants (n =2816) in a population survey of a random sample of men and women between 30 and 75 years of age in the municipalities of Vara (81% participation rate) and Skövde (70%), in western Sweden during 2001–2005.
Main outcome measures
Anthropometric measures, blood pressure, leisure-time physical activity, current smoking, fasting glucose, and cholesterol. Hypertension was defined as ongoing treatment for hypertension, or three consecutive blood pressure readings ≥140 systolic and/or ≥90 mmHg diastolic. Hypertension was considered controlled when the blood pressure was <140/90 mm Hg (both).
Results
The prevalence of hypertension was 20% in both men and women with a steep increase by age. Among hypertensive subjects, 33% were unaware, 36% aware but uncontrolled, and 31% aware and controlled, with no statistically significant differences between men and women. Patients with diabetes had a higher awareness (87% vs. 64%, p <0.001), but the same control rate (56% vs. 44%, p =0.133), when compared with those without diabetes.
Conclusion
A large proportion of subjects with hypertension are still unaware of their condition, or aware but not controlled. It is important to emphasize population-based prevention to reduce the prevalence of hypertension, to perform screening to increase awareness, and to improve implementation of expert guidelines in clinical practice to improve control.
doi:10.3109/02813432.2012.684207
PMCID: PMC3378010  PMID: 22643153
Awareness; control; hypertension; population survey; prevention
7.  Diastolic dysfunction is associated with sedentary leisure time physical activity and smoking in females only 
Objectives
Left ventricular diastolic dysfunction with preserved systolic function (DD-PSF) is associated with an increased risk of morbidity and mortality. Population-based surveys studying the associations between DD-PSF and lifestyle-associated risk factors, such as leisure time physical activity (LTPA) and smoking, are scarce. Thus, the aims were to explore the associations between DD-PSF and LTPA and smoking, employing optimal echocardiographic techniques.
Design
Cross-sectional study conducted from 2001 to 2003.
Setting
The study was conducted in a random sample of a rural Swedish population.
Subjects
Men and women of 30–75 years of age were consecutively invited for conventional echocardiography and tissue velocity imaging (n = 1149). Structured questionnaires and physical examinations were conducted using standardized methods.
Main outcome measures
DD-PSF was defined according to the European Society of Cardiology criteria excluding subjects with ejection fraction < 45%, or a self-reported history of heart failure.
Results
Complete information was available in 500 men and 538 women. In a multivariate model, DD-PSF was independently associated with sedentary LTPA and smoking in females; sedentary LTPA odds ratio (OR) 2.91, 95% confidence interval (CI) 1.02 to 8.27, and smoking OR 3.42, 95% CI 1.35 to 8.64. The probability of identifying DD-PSF in females with a sedentary LTPA was 37% and increased to 80% if they also had hypertension and were obese.
Conclusions
Sedentary LTPA and smoking are independently associated with DD-PSF in females. Identification of a sedentary lifestyle in females increases the probability of diagnosing DD-PSF.
doi:10.3109/02813432.2010.506803
PMCID: PMC3442333  PMID: 20698731
Echocardiography; gender; family practice; leisure time physical activity; smoking
8.  Salivary cortisol differs with age and sex and shows inverse associations with WHR in Swedish women: a cross-sectional study 
Background
Most studies on cortisol have focused on smaller, selected samples. We therefore aimed to sex-specifically study the diurnal cortisol pattern and explore its association with abdominal obesity in a large unselected population.
Methods
In 2001–2004, 1811 men and women (30–75 years) were randomly selected from the Vara population, south-western Sweden (81% participation rate). Of these, 1671 subjects with full information on basal morning and evening salivary cortisol and anthropometric measurements were included in this cross-sectional study. Differences between groups were examined by general linear model and by logistic and linear regression analyses.
Results
Morning and Δ-cortisol (morning – evening cortisol) were significantly higher in women than men. In both genders older age was significantly associated with higher levels of all cortisol measures, however, most consistently with evening cortisol. In women only, age-adjusted means of WHR were significantly lower in the highest compared to the lowest quartile of morning cortisol (p = 0.036) and Δ-cortisol (p < 0.001), respectively. Furthermore, when comparing WHR above and below the mean, the age-adjusted OR in women for the lowest quartile of cortisol compared to the highest was 1.5 (1.0–2.2, p = 0.058) for morning cortisol and 1.9 (1.3–2.8) for Δ-cortisol. All findings for Δ-cortisol remained after adjustments for multiple covariates and were also seen in a linear regression analysis (p = 0.003).
Conclusion
In summary, our findings of generally higher cortisol levels in women than men of all ages are novel and the stronger results seen for Δ-cortisol as opposed to morning cortisol in the association with WHR emphasise the need of studying cortisol variation intra-individually. To our knowledge, the associations in this study have never before been investigated in such a large population sample of both men and women. Our results therefore offer important knowledge on the descriptive characteristics of cortisol in relation to age and gender, and on the impact that associations previously seen between cortisol and abdominal obesity in smaller, selected samples have on a population level.
doi:10.1186/1472-6823-9-16
PMCID: PMC2711063  PMID: 19545400
9.  The Asp298 allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus 
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.
doi:10.1186/1471-2261-8-36
PMCID: PMC2636751  PMID: 19077211
10.  Predictors of acute myocardial infarction mortality in hypertensive patients treated in primary care 
Objective
To explore risk factors for acute myocardial infarction (AMI) mortality in hypertensive patients treated in primary care.
Design
Community-based cohort study.
Setting
Hypertension outpatient clinic in primary health care.
Subjects
Patients who consecutively underwent an annual follow-up during 1992–1993 (n =894; 377 men and 517 women).
Methods
All events of fatal AMI were ascertained by record linkage to the National Mortality Register to December 31, 2002. Gender-specific predictors for AMI mortality were analysed by Cox regression.
Main outcome measure
AMI mortality.
Results
During a mean follow-up of 8.7 years 32 cases (8.5%) of fatal AMI were observed in men and 31 cases (6.0%) were observed in women. Most important predictors for AMI mortality in men were microalbuminuria (HR 3.8, CI 1.8–8.0) and left ventricular hypertrophy (HR 4.0, CI 1.7–9.4), whilst in women type 2 diabetes (HR 4.8, CI 2.4–9.8) was an important predictor. In hypertensive patients without diabetes male gender was associated with high AMI mortality (HR 2.7, CI 1.4–5.3), but in patients with both hypertension and type 2 diabetes the higher risk in men disappeared (HR 0.8, CI 0.4–1.7).
Conclusion
Cardiovascular disease risk factors remain strong predictors of AMI mortality in hypertensive patients but with a different pattern in the two genders. Markers of organ damage are more important predictors in men, whereas markers of impaired glucose metabolism are more important predictors in women.
doi:10.1080/02813430701706253
PMCID: PMC3379766  PMID: 17965983
Acute myocardial infarction; cardiovascular disease risk factors; family practice; hypertension; primary care; type 2 diabetes
11.  Intranasal Immunization of Mice with Group B Streptococcal Protein Rib and Cholera Toxin B Subunit Confers Protection against Lethal Infection  
Infection and Immunity  2004;72(2):1184-1187.
Intranasal immunization of mice with Rib, a cell surface protein of group B streptococcus (GBS), conjugated to or simply coadministered with the recombinant cholera toxin B subunit, induces systemic immunoglobulin G (IgG) and local IgA antibody responses and confers protection against lethal GBS infection. These findings have implications for the development of a human GBS vaccine.
doi:10.1128/IAI.72.2.1184-1187.2004
PMCID: PMC321638  PMID: 14742572
12.  Group B Streptococcal Surface Proteins as Targets for Protective Antibodies: Identification of Two Novel Proteins in Strains of Serotype V 
Infection and Immunity  1999;67(12):6350-6357.
Strains of group B streptococcus (GBS) express surface proteins that confer protective immunity. In particular, most strains of the four classical capsular serotypes (Ia, Ib, II, and III) express either of the Rib and α proteins, two members of the same protein family. Here, we report a study of surface proteins expressed by strains of serotype V, which has recently emerged as an important serotype among GBS strains causing serious disease. Two novel GBS proteins were identified, purified, and characterized. One of these proteins, designated Fbs, was immunologically unrelated to other GBS surface proteins. This ∼110-kDa protein was found in 15 of 49 (31%) type V isolates but in few strains of other serotypes. The Fbs proteins expressed by different strains showed limited variation in size. The most common surface protein among type V strains, found in 29 of 49 (59%) isolates, was designated Rib-like, since it cross-reacted with Rib but was not immunologically identical to Rib. Characterization of this Rib-like protein showed that the N-terminal sequence (12 residues) was identical to that of α, although these two proteins lacked cross-reactivity. The biochemical and immunological properties of the Rib-like GBS protein indicate that it is closely related to the R28 protein of Streptococcus pyogenes. Importantly, passive and active immunization experiments with mice showed that the Fbs and Rib-like proteins are targets for protective antibodies. These two proteins are therefore of interest for analysis of pathogenic mechanisms and for vaccine development.
PMCID: PMC97041  PMID: 10569749

Results 1-12 (12)