We sought to determine levels of adherence in eight European countries to recommendations for the management of type 2 diabetes and to investigate factors associated with key intermediate outcomes.
RESEARCH DESIGN AND METHODS
GUIDANCE was a cross-sectional study including retrospective data extraction from the medical records of people with type 2 diabetes recruited, using a shared protocol, from primary and specialist care sites in the following eight European countries: Belgium, France, Germany, Italy, Ireland, Sweden, the Netherlands, and the United Kingdom. The dataset for analysis comprised 7,597 cases. Proportions meeting process and outcome criteria were determined, including between-country variations. Logistic regression was used to investigate potential predictors of meeting targets for HbA1c, blood pressure, and LDL cholesterol.
In the total sample, adherence to process recommendations was high for some measures, for example, HbA1c recorded in past 12 months in 97.6% of cases. Target achievement for intermediate outcome measures was lower, with only 53.6% having HbA1c <7%. Considerable between-country variation was identified for both processes and outcomes. The following characteristics were associated with an increased likelihood of meeting targets for all three measures considered (HbA1c, blood pressure, LDL cholesterol): shorter diagnosis of diabetes; having one or more macrovascular complications; lower BMI; being prescribed lipid-lowering medication; and no current antihypertensive prescribing.
Compared with earlier reports, we have suggested some encouraging positive trends in Europe in relation to meeting targets for the management of people with type 2 diabetes, but there is still scope for further improvement and greater between-country consistency.
Smoking, diabetes, male sex, hypercholesterolaemia and hypertension are well-established risk factors for the development of coronary artery disease (CAD). However, less is known about their role in influencing the outcome in the event of an acute coronary syndrome (ACS). The aim of this study was to determine if these risk factors are associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with suspected ACS.
Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992–1996).
From 5292 patients admitted to the coronary care unit, 908 patients aged 30–74 years were selected, who at discharge had received the diagnosis of either MI (527) or UA (381). A control group consisted of 948 patients aged 30–74 years in whom a diagnosis of ACS was excluded.
Main outcome measures
MI or UA.
Current smoking (OR 2.42 (1.61 to 3.62)), impaired glucose homoeostasis defined as glycated haemoglobin ≥5.5% + blood glucose ≥7.5 mM (OR 1.78 (1.19 to 2.67)) and male sex (OR 1.71 (1.21 to 2.40)) were significant factors predisposing to MI over UA, in the event of an ACS. Compared with the non-ACS group, impaired glucose homoeostasis, male sex, cholesterol level and age were significantly associated with development of an ACS (MI and UA). Interestingly, smoking was significantly associated with MI (OR 2.00 (1.32 to 3.02)), but not UA.
Smoking or impaired glucose homoeostasis is an acquired risk factor for a severe ACS outcome in patients with CAD. Importantly, smoking was not associated with UA, suggesting that it is not a risk factor for all clinical manifestations of CAD, but its influence is important mainly in the acute stages of ACS. Thus, on a diagnosis of CAD, the cessation of smoking and management of glucose homoeostasis are of upmost importance to avoid severe subsequent ACS consequences.
Increasing evidence on associations between mental health and chronic diseases like cardio-vascular disease and diabetes together with the fact that little is known about the prevalence of anxiety/depression and associated risk factors among Iraqi immigrants to Sweden, warrants a study in this group. The aim was to study the prevalence of anxiety and depression in immigrants from Iraq compared to native Swedes and compare socioeconomic and lifestyle-related factors associated with these conditions.
A population-based, cross-sectional study of residents of Malmö, Sweden, aged 30–75 years, born in Iraq or Sweden. The overall response rate was 49% for Iraqis and 32% for Swedes. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Associations were studied using multivariate logistic regression models. The outcome was odds of depression and/or anxiety.
Compared to Swedes (n = 634), anxiety was three times as prevalent (52.6 vs. 16.3%, p < 0.001) and depression five times as prevalent (16.3 vs. 3.1%, p < 0.001) in Iraqi immigrants (n = 1255). Iraqis were three times more likely to be anxious and/or depressed compared to Swedes (odds ratio (OR) 3.02, 95% confidence interval (CI) 2.06-4.41). Among Iraqis, physical inactivity (<150 min/week) (OR 2.00, 95% CI 1.49-2.69), economic insecurity (OR 2.16, 95% CI 1.56-3.01), inability to trust people (OR 1.75, 95% CI 1.28-2.39) and smoking (OR 1.43, 95% CI 1.02-2.01), were strongly associated with anxiety/depression. Among Swedes, living alone (OR 2.10, 95% CI 1.36-3.25) and economic insecurity (OR 2.38, 95% CI 1.38-4.12) showed the strongest associations with anxiety/depression. Country of birth modified the effect of physical inactivity (P
=0.058) as well as of marital status (P
Our study indicates that economic insecurity has a major impact on poor mental health irrespective of ethnic background but that physical inactivity may be more strongly associated with anxiety/depression in immigrants from the Middle East compared to native Swedes. Preventive actions emphasizing increased physical activity may reduce the risk of poor mental health in immigrants from the Middle East, however intervention studies are warranted to test this hypothesis.
Anxiety; Depression; Physical activity; Immigrants; Middle East; Sweden
There is a gap between prescribed asthma medication and diagnosed asthma in children and adolescents. However, few studies have explored this issue among adults, where asthma medication is also used for the treatment of chronic obstructive pulmonary disease (COPD). The aim of this study was to examine the relationship between prescribing of medications indicated for asthma and COPD and the recorded diagnosis for these conditions.
In a register-based study, individuals prescribed a medication indicated for asthma and COPD during 2004-2005 (Group A; n = 14 101) and patients with diagnoses of asthma or COPD recorded during 2000-2005 (Group B; n = 12 328) were identified from primary health care centers in Skaraborg, Sweden. From a 5% random sample of the medication users (n = 670), the written medical records were accessed. Primary outcomes: prevalence of medication and diagnoses, reasons for prescription. Secondary outcomes: type and number of prescribed drugs and performance of peak expiratory flow or spirometry.
Medications indicated for asthma and COPD was prescribed to 5.6% of the population in primary care (n = 14 101). Among them, an asthma diagnosis was recorded for 5876 individuals (42%), 1116 (8%) were diagnosed with COPD and 545 (4%) had both diagnoses. The remaining 6564 individuals (46%) were lacking a recorded diagnosis. The gap between diagnosis and medication was present in all age-groups. Medication was used as a diagnostic tool among 30% of the undiagnosed patients and prescribed off-label for 54%. Missed recording of ICD-codes for existing asthma or COPD accounted for 16%.
There was a large discrepancy between prescribing of medication and the prevalence of diagnosed asthma and COPD. Consequently, the prevalence of prescriptions of medications indicated for asthma and COPD should not be used to estimate the prevalence of these conditions. Medication was used both as a diagnostic tool and in an off-label manner. Therefore, the prescribing of medications for asthma and COPD does not adhere to national clinical guidelines. More efforts should be made to improve the prescribing of medication indicated for asthma and COPD so that they align with current guidelines.
Asthma; COPD; Prescribing; Off-label; Guidelines; Cross-sectional study
Body-mass index (BMI) has become the standard proxy for obesity in social science research. This study deals with the potential problems related to, first, relying on self-reported weight and height to calculate BMI (misreporting), and, second, the concern that BMI is a deficient measure of body fat (misclassification). Using a regional Swedish sample, we analyze whether socioeconomic disparities in BMI are biased because of misreporting, and whether socioeconomic disparities in the risk of obesity are sensitive to whether BMI or waist circumference is used to define obesity. Education and income are used as socioeconomic indicators. The overall conclusion is that misreporting and misclassification may indeed matter for estimated educational and income disparities in BMI and obesity. In the misreporting part we find that women with higher education misreport less than those with lower education, leading to underestimation of the education disparity when using self-reported information. In the misclassification part we find that the probability of being misclassified decreases with income, for both men and women. Among women, the consequence is a steeper income gradient when obesity is defined using waist circumference instead of BMI. Among men the income gradient is statistically insignificant irrespective of how obesity is defined, but when estimating the probability of obesity defined by waist circumference, an educational gradient, which is not present when classifying men using BMI, arises.
Misreporting; Misclassification; BMI; Obesity; Waist circumference; Education; Income; C18; I12; I14
Type 2 diabetes is highly prevalent in immigrants to Sweden from Iraq, but the prevalence of cardiovascular disease (CVD) and its risk factors are not known. In this survey we aimed to compare the prevalence of CVD and CVD-associated risk factors between a population born in Iraq and individuals born in Sweden.
This population-based, cross-sectional study comprised 1,365 Iraqi immigrants and 739 Swedes (age 30-75 years) residing in the same socioeconomic area in Malmö, Sweden. Blood tests were performed and socio-demography and lifestyles were characterized. To investigate potential differences in CVD, odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by multivariate logistic regression analysis with adjustment for metabolic, lifestyle and psychosocial risk factors for CVD. Outcome measures were odds of CVD.
There were no differences in self-reported prevalence of CVD between Iraqi- and Swedish-born individuals (4.0 vs. 5.5%, OR 0.9, 95% CI 0.4-1.8). However, the prevalence of type 2 diabetes was higher in Iraqi compared to Swedish participants (8.4 vs. 3.3%, OR = 4.2, 95% CI 2.6-6.7). Moreover, among individuals with type 2 diabetes, Iraqis had a higher prevalence of CVD (22.8 vs. 8.0%, OR = 4.2, 95% CI 0.9-20.0), after adjustment for age and sex. By contrast, among those without diabetes, immigrants from Iraq had a lower prevalence of CVD than Swedes (2.2 vs. 5.5%, OR = 0.6, 95% CI 0.3-0.9).
Type 2 diabetes was an independent risk factor for CVD in Iraqis only (OR = 6.8, 95% CI 2.8-16.2). This was confirmed by an interaction between country of birth and diabetes (p = 0.010). In addition, in Iraqis, type 2 diabetes contributed to CVD risk to a higher extent than history of hypertension (standardized OR 1.5 vs. 1.4).
This survey indicates that the odds of CVD in immigrants from Iraq are highly dependent on the presence or absence of type 2 diabetes and that type 2 diabetes contributes with higher odds of CVD in Iraqi immigrants compared to native Swedes. Our study suggests that CVD prevention in immigrants from the Middle East would benefit from prevention of type 2 diabetes.
Type 2 diabetes; Cardiovascular disease; Migration; Middle East
The increased incidence of impaired glucose tolerance (IGT), are serious public health issues, and several studies link sleeping disorders with increased risk of developing type 2 diabetes, impaired glucose tolerance and insulin resistance (IR). This study explore how self-reported lack of sleep and low vitality, are associated with IGT in a representative Swedish population.
A cross-sectional survey conducted in two municipalities in South-western Sweden. Participants aged 30–75 were randomly selected from the population in strata by sex and age. Altogether, 2,816 participants were surveyed with a participation rates at 76%. Participants with normal glucose tolerance (n=2,314), and those with IGT (n=213) were retained for analyses. The participants answered a questionnaire before the oral glucose tolerance test (OGTT). Associations for questions concerning sleeping disorders, vitality and IGT were analysed using logistic regression and were expressed as odds ratios (OR) with 95% CI.
In men a statistically significant age-adjusted association was found between self-reported lack of sleep and IGT: OR 2.4 (95% CI: 1.1-5.4). It did not weaken after further adjustment for body mass index (BMI), smoking, education, and leisure time physical activity 2.3 (1.0-5.5, p=0.044). No such associations were found in females. Corresponding age-adjusted associations between low vitality and IGT in both men 2.8 (1.3-5.8), and women 2.0 (1.2-3.4) were successively lost with increasing adjustment.
Insufficient sleep seems independently associated with IGT in men, while low vitality was not independently associated with IGT neither in men nor women, when multiple confounders are considered. IGT should be considered in patients presenting these symptoms, and underlying mechanisms further explored.
Impaired glucose tolerance; Fatigue; Sleeping disorders; Health conversation; Primary health care
To investigate gender differences in the association between self-rated health (SRH) and impaired glucose tolerance (IGT) in subjects unaware of their glucose tolerance.
A cross-sectional population-based study.
The two municipalities of Vara and Skövde in south-western Sweden.
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.
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).
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.
Gender; general practice; impaired glucose tolerance; self-rated health; Sweden
The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population.
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.
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).
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.
Sex hormone binding globulin (SHBG); Testosterone; Gender; Hypertension; BMI
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 = × 10−50) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 × 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 × 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 × 10−57) and GCK (rs4607517, P = 1.0 × 10−25) loci.
To investigate the impact on ICD coding behaviour of a new case-mix reimbursement system based on coded patient diagnoses. The main hypothesis was that after the introduction of the new system the coding of chronic diseases like hypertension and cancer would increase and the variance in propensity for coding would decrease on both physician and health care centre (HCC) levels.
Cross-sectional multilevel logistic regression analyses were performed in periods covering the time before and after the introduction of the new reimbursement system.
Skaraborg primary care, Sweden.
All patients (n = 76 546 to 79 826) 50 years of age and older visiting 468 to 627 physicians at the 22 public HCCs in five consecutive time periods of one year each.
Main outcome measures
Registered codes for hypertension and cancer diseases in Skaraborg primary care database (SPCD).
After the introduction of the new reimbursement system the adjusted prevalence of hypertension and cancer in SPCD increased from 17.4% to 32.2% and from 0.79% to 2.32%, respectively, probably partly due to an increased diagnosis coding of indirect patient contacts. The total variance in the propensity for coding declined simultaneously at the physician level for both diagnosis groups.
Changes in the healthcare reimbursement system may directly influence the contents of a research database that retrieves data from clinical practice. This should be taken into account when using such a database for research purposes, and the data should be validated for each diagnosis.
Electronic health records; general practice; ICD codes; incentive; multilevel analysis; primary health care; reimbursement; Sweden
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.
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.
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.
sex hormone-binding globulin; insulin; liver; diabetes
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.
To describe the prevalence, awareness, and control of hypertension in a Swedish population during the early 2000s to address implications for care and prevention.
A cross-sectional population survey.
Primary health care in Skaraborg, a rural part of western Sweden.
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).
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.
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.
Awareness; control; hypertension; population survey; prevention
Procedures documented by general practitioners in primary care have not been studied in relation to procedure coding systems. We aimed to describe procedures documented by Swedish general practitioners in electronic patient records and to compare them to the Swedish Classification of Health Interventions (KVÅ) and SNOMED CT.
Procedures in 200 record entries were identified, coded, assessed in relation to two procedure coding systems and analysed.
417 procedures found in the 200 electronic patient record entries were coded with 36 different Classification of Health Interventions categories and 148 different SNOMED CT concepts. 22.8% of the procedures could not be coded with any Classification of Health Interventions category and 4.3% could not be coded with any SNOMED CT concept. 206 procedure-concept/category pairs were assessed as a complete match in SNOMED CT compared to 10 in the Classification of Health Interventions.
Procedures documented by general practitioners were present in nearly all electronic patient record entries. Almost all procedures could be coded using SNOMED CT.
Classification of Health Interventions covered the procedures to a lesser extent and with a much lower degree of concordance. SNOMED CT is a more flexible terminology system that can be used for different purposes for procedure coding in primary care.
The aim of the study was to identify symptoms in people with impaired glucose tolerance (IGT) and describe their experiences of living with the symptoms which they related to their condition. Twenty-one participants, from a cross-sectional population-based study, diagnosed as having IGT, were invited for an interview. The interviews were analyzed in two phases by means of a manifest and latent content analysis. The narratives included seven categories of symptoms (and more than 25 different symptoms) presented by the respondents. This study shows that symptoms such as the patient's own interpretation of different perceptions in the body must be considered, as well as signs and/or objective observations. Symptoms ought to be seen as complementary components in the health encounter and health conversation. The results of this study indicate that health professionals should increase their awareness of the balance between the implicit and the explicit bodily sensations that individuals communicate. Further studies are needed.
In recent years, several primary care databases recording information from computerized medical records have been established and used for quality assessment of medical care and research. However, to be useful for research purposes, the data generated routinely from every day practice require registration of high quality. In this study we aimed to investigate (i) the frequency and validity of ICD code and drug prescription registration in the new Skaraborg primary care database (SPCD) and (ii) to investigate the sources of variation in this registration.
SPCD contains anonymous electronic medical records (ProfDoc III) automatically retrieved from all 24 public health care centres (HCC) in Skaraborg, Sweden. The frequencies of ICD code registration for the selected diagnoses diabetes mellitus, hypertension and chronic cardiovascular disease and the relevant drug prescriptions in the time period between May 2002 and October 2003 were analysed. The validity of data registration in the SPCD was assessed in a random sample of 50 medical records from each HCC (n = 1200 records) using the medical record text as gold standard. The variance of ICD code registration was studied with multi-level logistic regression analysis and expressed as median odds ratio (MOR).
For diabetes mellitus and hypertension ICD codes were registered in 80-90% of cases, while for congestive heart failure and ischemic heart disease ICD codes were registered more seldom (60-70%). Drug prescription registration was overall high (88%). A correlation between the frequency of ICD coded visits and the sensitivity of the ICD code registration was found for hypertension and congestive heart failure but not for diabetes or ischemic heart disease.
The frequency of ICD code registration varied from 42 to 90% between HCCs, and the greatest variation was found at the physician level (MORPHYSICIAN = 4.2 and MORHCC = 2.3).
Since the frequency of ICD code registration varies between different diagnoses, each diagnosis must be separately validated. Improved frequency and quality of ICD code registration might be achieved by interventions directed towards the physicians where the greatest amount of variation was found.
The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α2B-, β1-, and β2-adrenergic receptor genes and obstructive sleep apnea (OSA) in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β1-adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02–4.7). Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95% CI 1.4–21.2).
To identify novel genetic loci associated with fasting glucose concentrations, we examined the leading association signals in 10 genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding the 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=3.2×10−50) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P=1.1×10−15). 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=3.3×10−7) in a meta-analysis of thirteen case-control studies totalling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P=1.1×10−57) and GCK (rs4607517, P=1.0×10−25) loci.
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.
Cross-sectional study conducted from 2001 to 2003.
The study was conducted in a random sample of a rural Swedish population.
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.
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.
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.
Echocardiography; gender; family practice; leisure time physical activity; smoking
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.
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.
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).
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.
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.
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.
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.
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.
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).
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.
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.
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.
To determine the importance of IgM antibodies against phosphorylcholine (aPC), a novel protective factor for cardiovascular disease (CVD), in a population with a non-western life style as compared with a Swedish control group.
Methods and results
Risk factors for cardiovascular disease were determined in a group of 108 individuals aged 40–86 years from New Guinea and 108 age-and sex-matched individuals from a population based study in Sweden. Antibodies were tested by ELISA. aPC IgM levels were significantly higher among New Guineans than among Swedish controls (p < 0.0001). This difference remained significant among both men and women when controlled for LDL and blood pressure which were lower and smoking which was more prevalent in New Guineans as compared to Swedish controls (p < 0.0001). aPC IgM was significantly and negatively associated with age and systolic blood pressure among Swedish controls and with waist circumference among New Guineans. aPC IgM levels were significantly higher among women than men in both groups. The proportion of the saturated fatty acid (FA) myristic acid in serum cholesterol esters was negatively but polyunsaturated eicosapentaenoic acid and also lipoprotein (a) were positively associated with aPC IgM levels.
IgM-antibodies against PC, which have atheroprotective properties, are higher in a population from Kitava, New Guinea with a traditional lifestyle, than in Swedish Controls, and higher among women than men in both populations tested. Such antibodies could contribute to the low incidence of cardiovascular disease reported from Kitava and could also provide an explanation as to why women have a later onset of CVD than men.
To explore risk factors for acute myocardial infarction (AMI) mortality in hypertensive patients treated in primary care.
Community-based cohort study.
Hypertension outpatient clinic in primary health care.
Patients who consecutively underwent an annual follow-up during 1992–1993 (n =894; 377 men and 517 women).
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
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).
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.
Acute myocardial infarction; cardiovascular disease risk factors; family practice; hypertension; primary care; type 2 diabetes