Vidar Hjellvik

Heart rate and mortality from cardiovascular causes : a 12 year follow-up study of 379 843 men and women aged 40-45 years

AIM To study the relationship between heart rate and (a) all deaths and (b) cardiovascular deaths in a large cohort of middle-aged Norwegian men and women. METHODS AND RESULTS A prospective study of participants in cardiovascular surveys that were carried out in 1985-1999 and covered men and women aged 40-45 years in all counties except the capital, Oslo. In total, 180,353 men and 199,490 women aged 40-45 years without cardiovascular history or diabetes accrued 4 775 683 years of follow-up. There was a positive and graded association between heart rate and mortality from all causes, as well as between heart rate and deaths from cardiovascular disease (CVD), ischaemic heart disease, and stroke. However, these associations were greatly reduced when we adjusted for the main risk factors of disease. The hazard ratios for any death were reduced from 3.14 to 1.82 for men (95% CI, 1.62-2.04) and from 2.14 to 1.37 for women (95% CI, 1.19-1.59), when we compared > or =95 b.p.m. with <65 b.p.m. The corresponding figures for CVD were a reduction from 4.79 to 1.51 for men (95% CI, 1.21-1.87) and from 2.68 to 0.78 for women (95% CI, 0.53-1.15). CONCLUSION In this cohort of middle-aged men and women, a crude association between heart rate and death from CVDs was greatly weakened when we adjusted for the main risk factors of disease. This suggests that an increased heart rate in middle age may be a marker of high cardiovascular risk, but is not an independent risk factor.

Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

Background: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies. Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

Midlife vascular risk factors and their association with dementia deaths: results from a Norwegian prospective study followed up for 35 years.

There is growing evidence that midlife risk factors for vascular disease also are risk factors for dementia, but there is still need for long-term observational studies to address this. Our objective was to investigate the association of midlife vascular disease risk factors with dementia death. Participants were included in The Norwegian Counties Study (NCS) in the period 1974-78, aged 35-50 years at baseline. Information from NCS was linked with the Cause of Death Registry through the year 2009 using the unique personal identification number. The study included 48,793 participants, 1.5 million person years and 486 dementia deaths (187 Alzheimers; 299 non-Alzheimers dementia). Cox regression for cause-specific hazards was used. Dementia death was associated with increased total cholesterol levels (>7.80 vs. <5.20 mmol/l: HR=2.01, 95% confidence interval 1.37-2.93); diabetes (HR=2.43, 95% CI 1.40-4.32) and low body mass index (<20 kg/m(2) vs. 20-25 kg/m(2): HR=1.76, 95% CI 1.15-2.68) in midlife. The associations remained after adjustment for other vascular risk factors and educational level. Smoking status or blood pressure in midlife was not significantly associated with risk of dementia death, although the results indicate a possible increased risk in heavy smokers. People suffering from high cholesterol levels, diabetes or underweight in midlife are at increased risk of dying from or with dementia later in life. Our findings add to previous results suggesting that intervention in midlife may be important. To better understand the mechanisms involved in the associations between midlife underweight, diabetes, and elevated cholesterol level and late-life dementia death, these links need to be further investigated.

Body mass index as predictor for asthma: a cohort study of 118,723 males and females

The objective of the present study was to quantify the relationship between body mass index (BMI; in kilogrammes per metre squared) and asthma in middle-aged males and females, and to evaluate change in BMI as a risk factor for asthma. Asthma incidence was estimated from data on redeemed prescriptions of anti-asthmatic drugs during the period 2004–2007, retrieved from the nationwide Norwegian Prescription Database. BMI was measured during health surveys in 1994–1999 in >100,000 individuals born during 1952–1959. Change in BMI was based on self-report. Relative risks were estimated using Poisson regression. The relative risk associated with a 3-unit increase in BMI ranged from 1.14 (95% confidence interval 1.10–1.18) in current smokers to 1.27 (1.22–1.32) in never-smokers after adjusting for confounders. The relative risk associated with a 3-unit increase in BMI was 1.21 (1.16–1.26) after adjusting for confounders, including sex, smoking and BMI. Asthma incidence, as measured by anti-asthmatic drug use, was positively related to both BMI and change in BMI. For BMI, the association was stronger for never-smokers than for ex-smokers and current smokers.

Body mass index, triglycerides, glucose, and blood pressure as predictors of type 2 diabetes in a middle-aged Norwegian cohort of men and women.

Background Obesity, hypertension, and hypertriglyceridemia are important risk factors for type 2 diabetes (T2D). We wanted to assess the risk associated with these three factors alone and in combination, and the relative importance of these and several other risk factors (eg, nonfasting glucose) as predictors of T2D. Methods Risk factors in a Norwegian population (n = 109,796) aged 40–45 years were measured in health studies in 1995–1999. Blood glucose-lowering drugs dispensed in 2004–2009 were used to estimate the incidence of T2D. Groups based on combinations of body mass index (BMI), diastolic blood pressure, and triglycerides were defined by using the 50% and 90% quantiles for each variable for men and women. The relative importance of BMI, triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose, blood pressure, and year of birth for predicting T2D was assessed using deviance from univariate and multivariate logistic regression models. Height, weight, and blood pressure were measured. All biomarkers were measured in nonfasting blood samples. Results In the various groups of BMI, triglycerides, and diastolic blood pressure, the incidence of T2D ranged from 0.5% to 19.7% in men and from 0.15% to 21.8% in women. BMI was the strongest predictor of incident T2D, followed by triglyceride levels in women and glucose levels in men. The inclusion of risk factors other than BMI, glucose, triglycerides, and blood pressure in multivariate models only marginally improved the prediction. Conclusion BMI was the strongest predictor of type 2 diabetes. At defined levels of BMI, the incidence of T2D varied substantially with triglyceride levels and blood pressure. Thus, controlling triglycerides and blood pressure in middle-aged individuals should be targeted to prevent later onset of T2D.

CARING (CAncer Risk and INsulin analoGues): The Association of Diabetes Mellitus and Cancer Risk with Focus on Possible Determinants - A Systematic Review and a Meta-Analysis

Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.

Coffee intake and oral–oesophageal cancer: follow-up of 389 624 Norwegian men and women 40–45 years

Background:The evidence on the relationship between coffee intake and cancer of the oral cavity and oesophagus is conflicting and few follow-up studies have been done.Methods:A total of 389 624 men and women 40–45 years who participated in a national survey programme were followed with respect to cancer for an average of 14.4 years by linkage to the Cancer Registry of Norway. Coffee consumption at baseline was reported as a categorical variable (0 or <1 cup, 1–4, 5–8, 9+ cups per day).ResultsAltogether 450 squamous oral or oesophageal cancers were registered during follow-up. The adjusted hazard ratios with 1–4 cups per day as reference were 1.01 (95% confidence interval: 0.70, 1.47), 1.16 (0.93, 1.45) and 0.96 (0.71, 1.14) for 0 or <1 cup, 5–8 and 9+ cups per day, respectively. Stratification by sex, type of coffee, smoking status and dividing the end point into oral and oesophageal cancers gave heterogeneous and non-significant estimates.Conclusion:This study does not support an inverse relationship between coffee intake and incidence of cancer in the mouth or oesophagus, but cannot exclude a weak inverse relationship.

Boiled Coffee Intake and Subsequent Risk for Type 2 Diabetes

Background: Many studies have found an inverse association between consumption of filtered coffee and incident type 2 diabetes. The effect of boiled coffee has been less studied. Methods: Information on self-reported coffee consumption was available from health surveys conducted from 1985 to 1999. We estimated type 2 diabetes incidences from redeemed prescriptions of oral antidiabetic drugs in the period 1 January 2004 to 1 January 2008. Results: With less than 1 cup/day as the reference, the relative risks associated with 1–4, 5–8, and 9 or more cups of boiled coffee per day were 0.87 (95% confidence interval = 0.80–0.95), 0.65 (0.59–0.72), and 0.65 (0.57–0.74), respectively, after adjusting for confounders. The corresponding relative risks associated with other types of coffee (mainly filtered) were 0.84 (0.79–0.90), 0.67 (0.62–0.71) and 0.62 (0.56–0.68). Conclusions: A moderate inverse association was found between consumption of both boiled and other types of coffee at the age of 40–45 years and the risk of being prescribed oral antidiabetic drugs 5–20 years later.

Self-reported Mental Health and Its Gender Differences as a Predictor of Suicide in the Middle-Aged

Studies of clinical cohorts and retrospective reports have identified psychiatric disorders as paramount risk factors for suicide. Much less is known about how self-reported mental health is related to completed suicide. To study the relation between self-reported mental health and risk of completed suicide, the authors prospectively followed a population-based Norwegian cohort of 61,588 men and 69,774 women aged 39-44 years for an average of 10.4 years between 1994 and 2007. Self-reported mental health was measured using an instrument based on the Hopkins Symptom Checklist and the General Health Questionnaire. Completed suicides were registered in the official Norwegian Cause of Death Registry. Females reported higher levels of mental distress than males. In comparison with persons reporting the fewest mental health symptoms, the adjusted hazard ratio for suicide increased from 1.8 (95% confidence interval (CI): 1.1, 2.9) in the moderately depressed group to 8.9 (95% CI: 4.4, 18.2) in the most depressed group. The risk difference was greatest in males. At each level of the mental health index, males had double the risk of suicide of females (hazard ratio = 2.3, 95% CI: 1.5, 3.3). This study shows a dose-response effect of self-reported mental health problems on completed suicide and replicates the gender paradox observed in the general population with prospective data.

Mental disorder diagnoses among children and adolescents who use antipsychotic drugs.

Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls.