Margareta Norberg

The Västerbotten Intervention Programme: background, design and implications.

Background and objective: In Sweden, mortality from cardiovascular diseases (CVD) increased steadily during the 20th century and in the mid-1980s it was highest in the county of Västerbotten. Therefore, a community intervention programme was launched – the Västerbotten Intervention Programme (VIP) – with the aim of reducing morbidity and mortality from CVD and diabetes. Design : The VIP was first developed in the small municipality of Norsjö in 1985. Subsequently, it was successively implemented across the county and is now integrated into ordinary primary care routines. A population-based strategy directed towards the public is combined with a strategy to reach all middle-aged persons individually at ages 40, 50 and 60 years, by inviting them to participate in systematic risk factor screening and individual counselling about healthy lifestyle habits. Blood samples for research purposes are stored at the Umeå University Medical Biobank. Results: Overall, 113,203 health examinations have been conducted in the VIP and 6,500–7,000 examinations take place each year. Almost 27,000 subjects have participated twice. Participation rates have ranged between 48 and 67%. A dropout rate analysis in 1998 indicated only a small social selection bias. Cross-sectional, nested case-control studies and prospective studies have been based on the VIP data. Linkages between the VIP and local, regional and national databases provide opportunities for interdisciplinary research, as well as national and international collaborations on a wide range of disease outcomes. A large number of publications are based on data that are collected in the VIP, many of which also use results from analysed stored blood samples. More than 20 PhD theses have been based primarily on the VIP data. Conclusions: The concept of the VIP, established as a collaboration between politicians and health care providers on the one hand and primary care, functioning as the operating machinery, and the public on the other, forms the basis for effective implementation and endurance over time. After more than 20 years of the VIP, there is a large comprehensive population-based database, a stable organisation to conduct health surveys and collect data, and a solid structure to enable widespread multidisciplinary and scientific collaborations.

The risk of venous thromboembolism is markedly elevated in patients with diabetes

Aims/hypothesisDiabetes mellitus is associated with several changes in coagulation and fibrinolysis that may lead to a thrombogenic propensity. However, it is not known whether these perturbations actually cause increased risk of venous thromboembolism.MethodsIn a retrospective population-based study we evaluated the medical records of all 302 adult patients who were admitted to the Umeå University Hospital with verified deep vein thrombosis or pulmonary embolism during the years 1997 to 1999. The patients were classified as diabetic (n=56) and non-diabetic (n=246) according to clinical information. The total number of diagnosed diabetic patients in different age groups in the catchment area was obtained from computerised registries in the primary health care centres and the Umeå University Hospital, and data on the background population were collected from the Swedish population registry.ResultsThe annual incidence rate of venous thromboembolism among diabetic patients in the population was 432 per 100,000 individuals (95% CI 375–496). In non-diabetic individuals it was 78 (95% CI 68–88). The age-adjusted incidence rate among the diabetic population was 274 (95% CI 262–286). The annual incidence rate of venous thromboembolism was elevated in type 1 and type 2 diabetic patients and the incidence rates were 704 (95% CI 314–1,566) and 412 (95% CI 312–544) respectively. The overall standardised morbidity ratio was 2.27 (95% CI 1.75–2.95), i.e. diabetic patients were more prone to venous thromboembolism after adjustment for age differences.Conclusions/interpretationThese results suggest that the age-adjusted risk for venous thromboembolism is more than two-fold higher among diabetic patients than in the non-diabetic background population.

A combination of HbA1c, fasting glucose and BMI is effective in screening for individuals at risk of future type 2 diabetes: OGTT is not needed.

Objective.  To identify a screening model that predicts high risk of future type 2 diabetes and is useful in clinical practice.

Fish consumption and myocardial infarction: a second prospective biomarker study from northern Sweden

BACKGROUND A beneficial role of fish consumption on the risk of myocardial infarction (MI) has been reported and is mostly ascribed to n-3 (omega-3) fatty acids. However, fish also contains methylmercury, which may increase the risk of MI. OBJECTIVE The objective was to determine how fish consumption and erythrocyte concentrations of mercury (Ery-Hg) and selenium (Ery-Se) are related to the risk of MI and whether n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) in plasma phospholipids (P-EPA+DHA) are protective. DESIGN This was a case-control study nested within the northern Sweden cohort, in which data and samples were collected prospectively. The study included 431 cases with an MI after data and sample collection, including 81 sudden cardiac deaths (SCDs) and 499 matched controls. Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses. RESULTS Odds ratios for the third compared with the first tertile were 0.65 (95% CI: 0.46, 0.91) for Ery-Hg, 0.75 (95% CI: 0.53, 1.06) for Ery-Se, and 0.78 (95% CI: 0.54, 1.11) for P-EPA+DHA. Ery-Hg and P-EPA+DHA were intercorrelated (Spearmans R = 0.34). No association was seen for reported fish consumption. Multivariate modeling did not change these associations significantly. Sex-specific analyses showed no differences in risk associations. High concentrations of Ery-Se were associated with an increased risk of SCD. CONCLUSIONS The biomarker results indicate a protective effect of fish consumption. No harmful effect of mercury was indicated in this low-exposed population in whom Ery-Hg and P-EPA+DHA were intercorrelated.

Contribution of Swedish moist snuff to the metabolic syndrome: a wolf in sheep's clothing?

Aim: Combined effects of genetic and environmental factors underlie the clustering of cardiovascular risk factors in the metabolic syndrome (MetSy). The aim was to investigate associations between several lifestyle factors and MetSy, with a focus on the possible role of smokeless tobacco in the form of Swedish moist snuff (snus). Methods: A population-based longitudinal cohort study within the Västerbotten Intervention Programme in Northern Sweden. All inhabitants at the ages of 30, 40, 50, and 60 are invited to participate in a health survey that includes a questionnaire on psychosocial conditions and lifestyle and measurement of biological variables. Individuals examined in 1990—94 (n=24,230) and who also returned for follow-up after 10 years were included (total of 16,492 individuals: 46.6% men and 53.4% women). Regression analyses were performed. MetSy was the outcome and analyses were adjusted for age, sex, alcohol abuse, and family history of CVD and diabetes. Results: Ten-year development of MetSy was associated with high-dose consumption of snus at baseline (OR 1.6 [95% CI 1.26—2.15]), low education (2.2 [1.92—2.63]), physical inactivity (1.5 [1.22—1.73]) and former smoking (1.2 [1.06—1.38]). Snus was associated with separate components of MetSy, including triglycerides (1.6, 1.30—1.95), obesity (1.7 [1.36—2.18]) but not hypertension, dysglycemia and low HDL cholesterol. Conclusions: MetSy is independently associated with high consumption of snus, even when controlling for smoking status. The finding is of public health interest in societies with widespread use of snus. More research is needed to better understand the mechanisms underlying this effect.

Soluble CD36 (sCD36) Clusters with Markers of Insulin Resistance, and High sCD36 Is Associated with Increased Type 2 Diabetes Risk

CONTEXT AND OBJECTIVE Soluble CD36 (sCD36) may be an early marker of insulin resistance and atherosclerosis. The objective of this prospective study was to evaluate sCD36 as a predictor of type 2 diabetes and to study its relationship with components of the metabolic syndrome (MetSy). DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: We conducted a case-referent study nested within a population-based health survey. Baseline variables included sCD36, body mass index, blood pressure, blood lipids, adipokines, inflammatory markers, and beta-cell function. A total of 173 initially nondiabetic cohort members who developed type 2 diabetes during 10 yr of follow-up were matched (1:2) with referents. Exploratory factor analysis was applied to hypothesize affiliation of sCD36 to the MetSy components. RESULTS Doubling of baseline sCD36 increases the odds ratio for diabetes development by 1.24 in the general study population and by 1.45 in the female population (P < 0.025). Comparing upper sCD36 quartiles with lower, odds ratio for diabetes was 4.6 in women (P = 0.001), 3.15 in men (P = 0.011), and 2.6 in obese individuals (P < 0.025). Multivariate analysis shows that sCD36 does not predict diabetes independent of fasting plasma glucose and insulin. Factor analysis of 15 variables generates a six-factor model explaining 66-69% of total variance, where sCD36, body mass index, insulin, proinsulin, and leptin were assigned to the obesity/insulin resistance cluster. CONCLUSIONS Upper quartile sCD36 is associated with elevated diabetes risk independent of age, gender, and obesity. Baseline sCD36 does not, however, predict diabetes independent of fasting glucose and insulin. sCD36 clusters with important markers of insulin resistance and MetSy that are key predictors of type 2 diabetes.

Changing patterns of tobacco use in a middle-aged population: the role of snus, gender, age, and education.

Background : In Sweden, the smoking prevalence has declined. In 2007, it was among the lowest in the industrialized world. A steady increase in the use of Swedish oral moist snuff, snus, has occurred in parallel. This development is neither solicited by authorities nor the medical establishment, but rather has occurred along with increased awareness of the dangers of smoking, and has been promoted by product development and marketing of snus. Objective : To evaluate time trends in patterns of tobacco use in northern Sweden during 1990–2007. Design : Cross-sectional (99,381 subjects) and longitudinal (26,867 subjects) data from the Västerbotten Intervention Programme (VIP) 1990–2007 were analyzed. All adults in Västerbotten County are invited to a VIP health examination at ages 40, 50, and 60 years, and until 1995 also 30 years. Smoking and use of snus were evaluated by gender, age and educational groups. Intermittent smoking was categorized as smoking. Results : From the period 1990–1995 to the period 2002–2007, smoking prevalence decreased from 26 to 16% among men and from 27 to 18% among women. The differences in prevalence increased between educational groups. The decline in smoking was less and the increase of snus use was greater among those with basic education. The use of snus among basic-educated 40-year-olds reached 35% among men and 14% among women during 2002–2007. Dual smoking and snus use increased among men and women with basic education. Smoking without snus use was more prevalent among women. Gender differences in total smoking prevalence (smoking only plus dual use) were small in all age groups, but increased among those with basic education reaching 7.3% during 2002–2007, with women being more frequent smokers. Smoking prevalences were similar among never, former and current snus users. Among the 30,000 former smokers, 38% of men and 64% of women had never used snus. Longitudinal data showed a decline in total tobacco use from baseline until follow-up and this was mainly due to a smoking cessation rate of < 1% a year. Snus use was started by 6.2% of the 30-year-old women (age at baseline), and this contributed to a stable prevalence of total tobacco use in this group. Seventy percent of baseline snus users still used snus at follow-up. Among smokers, 55% continued smoking, 12% of men and 7% of women switched to snus. Among those with dual tobacco use at baseline, a third of men and a fourth of women remained dual users 10 years later. Conclusion : There are increasing differences in tobacco use between educational groups. Higher smoking and snus use prevalence are found among those with basic education, and this is most pronounced in the younger group of this middle-aged population. In spite of a higher prevalence of smoking without snus use among women, total smoking prevalence is similar in men and women due to a higher prevalence of dual tobacco use, i.e. snus and cigarettes, among men. The increase in snus use is being paralleled by a slight increase in dual use and the smoking prevalence does not seem to be influenced by snus. This should be the subject of further studies and also have implications for tobacco control policies.

The obesity epidemic slows among the middle-aged population in Sweden while the socioeconomic gap widens

Background: Obesity prevalence has continuously increased in Northern Sweden as elsewhere. A cohort effect has been shown and an increasing proportion of the middle-aged population is maintaining body weight. Objective: To test the hypothesis that the obesity epidemic continues but at different speeds that are dependent on socioeconomic status. Design: Cross-sectional (103,940 adults) and longitudinal (26,872 adults) data from the Västerbotten Intervention Program 1990–2007 were included. All adults in Västerbotten County are invited to a health examination at the ages of 40, 50, and 60 years. Body mass index (BMI) and socioeconomic status, assessed by residence location, marital status, and education were evaluated. Results: BMI increased in all groups but was greater among men. During 1990–1995 and 2002–2007, mean BMIs were 25.9 and 26.8 among men and 25.2 and 25.9 among women. The trend of increasing BMI slowed around the year 2000 (p<0.001), but this was only observed among the highly educated adults in the most urbanized area. The difference between educational groups increased throughout the study period (men p=0.014, women p=0.002). Longitudinal data for both sexes showed a twofold higher baseline prevalence of obesity among individuals with basic compared to high education and it nearly doubled in all groups during the 10-year follow-up. Low education, living in a rural environment, and living alone were independent predictors of obesity development. The overall cumulative 10-year incidence was 9.4% in men, 9.1% in women, and twofold higher among those with basic and mid-level education who live in rural areas compared to those with high education who live in cities. Conclusion: The trend of increasing obesity has slowed in this middle-aged Northern Sweden population, but this trend shift occurred primarily among those with high education who live in an urban environment. Greater efforts to combat obesogenic environments are needed and should take socioeconomic and sociocultural aspects into account.

Trends of blood pressure levels and management in Västerbotten County, Sweden, during 1990-2010

Background: Availability of longitudinal data on hypertension and blood pressure levels are important to assess changes over time at the population level. Moreover, detailed information in different population sub-groups is important to understand inequity and social determinants of blood pressure distribution in the population. Objectives: The objectives of this study are to: (1) describe the trends of population blood pressure levels in men and women between different educational levels and geographic areas in Sweden during 1990–2010; (2) identify prevalences of hypertension, awareness, treatment, and control in the population; and (3) assess the 10-year risk of developing hypertension among individuals with normal and high normal blood pressures. Methods: This study is based on data from the Västerbotten Intervention Program (VIP) in Västerbotten County, Sweden. The cross-sectional analysis includes 133,082 VIP health examinations among individuals aged 30, 40, 50, and 60 years from 1990 to 2010. The panel analysis includes 34,868 individuals who were re-examined 10 years after the baseline examination. Individuals completed a self-administered health questionnaire that covers demographic and socio-economic information, self-reported health, and lifestyle behaviours. Blood pressure measurement was obtained prior to the questionnaire. In the cross-sectional analysis, trends of blood pressure by sex, and between educational groups and geographic areas are presented. In the panel analysis, the 10-year risk of developing hypertension is estimated using the predicted probability from logistic regression analysis for each sex, controlling for age and educational level. Results: The prevalence of hypertension decreased from 1990 to 2010; from 43.8 to 36.0% (p < 0.001) among men, and 37.6 to 27.5% among women (p < 0.001). Individuals with basic education had a significantly higher prevalence of hypertension compared to those with medium or high education. Although the decreases were observed in all geographic areas, individuals in rural inland areas had a much higher prevalence compared to those who lived in Umeå City. The proportion of hypertensive women who were aware of their hypertension (61.7%) was significantly higher than men (51.6%). About 34% of men and 42% of women with hypertension reported taking blood pressure medication. Over time, awareness and control of hypertension improved (from 46.5% in 1990 to 69% in 2010 and from 30 to 65%, respectively). The gaps between educational groups diminished. This study shows a significantly higher risk of developing hypertension for men and women with high normal blood pressure compared to those with normal blood pressure at baseline in all age cohorts and educational groups. The average risks of developing hypertension among men with high normal blood pressure were 21.5, 45.8, and 56.3% in the 30, 40, and 50-year cohorts, respectively. Corresponding numbers for women were 22.6, 47.4, and 57.9%. Conclusions: Levels of blood pressure and hypertension decreased significantly among the Västerbotten population in the last 21 years. Hypertension management has improved and there is increased awareness, treatment, and control of blood pressure. Despite these achievements, the persisting social gaps in blood pressure levels and management demand further investigation and action from policy makers. Future research should attempt to identify and address the root causes of these health inequities to ensure better and equal health for the whole population.

The Impact of Leptin and Adiponectin on Incident Type 2 Diabetes Is Modified by Sex and Insulin Resistance

BACKGROUND Adiponectin and leptin and their ratio have been associated with incident type 2 diabetes (T2DM), although the data presented are conflicting and the populations studied have been small. In this large, prospective, nested, case referent study, we hypothesized that these associations are sex specific and may be modified by insulin resistance. METHODS Men and women aged 30-60 years with incident T2DM (n=640) and a prior health survey within the Västerbotten Intervention Programme (VIP) and matched referents (n=1564) were identified. Using conditional logistic regression analyses, we tested whether baseline plasma adiponectin and leptin levels and their ratio independently predicted incident T2DM, stratified for gender and insulin resistance. RESULTS Adjusted for traditional risk factors, fourth-quartile levels of adiponectin were associated with a reduced risk of T2DM in men [odds ratio (OR) 0.55 (0.36-0.86)] and women [OR 0.47 (0.27-0.83)]. Quartile four of the leptin/adiponectin ratio predicted T2DM in both men [OR 3.08 (1.68-5.67)] and women [OR 3.31 (1.56-7.03)], whereas quartile-four levels of leptin predicted T2DM only in men [OR 2.30 (1.32-4.02)]. When stratified for insulin sensitivity and adjusted for body mass index (BMI), log(e)-transformed leptin predicted T2DM in insulin-sensitive men [OR 1.56 (1.13-2.17)] but not in insulin-resistant men [OR 1.03 (0.76-1.39)]. The effect of adiponectin and the leptin/adiponectin ratio was not influenced by the insulin sensitivity status. CONCLUSIONS Leptin in men and adiponectin in both sexes were independent predictors of T2DM. The association was modified by the degree of insulin sensitivity. The leptin/adiponectin ratio may add predictive information beyond the separate hormones.