Egil Arnesen

The Tromsø Heart Study

We examined the relation between coffee consumption and levels of serum total cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglycerides in a population of 7213 women and 7368 men between the ages of 20 and 54 years. Coffee consumption was positively associated with levels of total cholesterol and triglycerides in both sexes and was inversely associated with levels of HDL cholesterol in women. The coffee-cholesterol relation remained strong and statistically significant (P less than 0.0001 in a covariance analysis) after adjustment for age, logarithm of body-mass index, physical activity in leisure time, cigarette smoking, and alcohol consumption. After adjustment for all covariates, the total cholesterol level was 5.56 +/- 0.05 mmol per liter (mean +/- S.E.) in men drinking less than one cup of coffee a day, as compared with 6.23 +/- 0.03 mmol per liter in those consuming more than nine cups a day. The corresponding figures for women were 5.32 +/- 0.05 and 5.92 +/- 0.04 mmol per liter. None of the other variables considered could explain this relation. We conclude that coffee consumption is a major contributor to the variation in levels of total cholesterol.

A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR]=1.23, 95% confidence interval [CI]=1.13-1.33, p=3.02x10(-7)), but not with other histologic types (OR=1.01, p=0.84 and OR=1.00, p=0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR=1.24, 95% CI=1.17-1.31, p=3.74x10(-14) for AD; OR=0.99, p=0.69 and OR=0.97, p=0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.

Vascular Factors and Risk of Dementia: Design of the Three-City Study and Baseline Characteristics of the Study Population

Objective: To describe the baseline characteristics of the participants in the Three-City (3C) Study, a study aiming to evaluate the risk of dementia and cognitive impairment attributable to vascular factors. Methods: Between 1999 and 2001, 9,693 persons aged 65 years and over, noninstitutionalized, were recruited from the electoral rolls of three French cities, i.e. Bordeaux, Dijon and Montpellier. Health-related data were collected during face-to-face interviews using standardized questionnaires. The baseline examination included cognitive testing and diagnosis of dementia, and assessment of vascular risk factors, including blood pressure measurements, ultrasound examination of the carotid arteries, and measurement of biological parameters (glycemia, total, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinemia); 3,442 magnetic resonance imaging (MRI) examinations were performed in subjects aged 65–79. Measurements of ultrasound, blood, and MRI parameters were centralized. Two follow-up examinations (at 2 and 4 years) were planned. Results: After exclusion of the participants who had subsequently refused the medical interview, the 3C Study sample consisted of 3,649 men (39.3%) and 5,645 women, mean age 74.4 years, with a relatively high level of education and income. Forty-two percent of the participants reported to be followed up for hypertension, about one third for hypercholesterolemia, and 8% for diabetes; 65% had elevated blood pressure measures (systolic blood pressure ≧140 or diastolic blood pressure ≧90). The proportion of Mini-Mental State Examination scores below 24 was 7% and dementia was diagnosed in 2.2% of the participants. Conclusion: Distribution of baseline characteristics of the 3C Study participants suggests that this study will provide a unique opportunity to estimate the risk of dementia attributable to vascular factors.

Smoking, Serum Lipids, Blood Pressure, and Sex Differences in Myocardial Infarction A 12-Year Follow-up of the Finnmark Study

BACKGROUND Few epidemiological studies have investigated the relative importance of major coronary risk factors in the two sexes within the same study population. In particular, it is not clear whether smoking carries a similar risk of coronary heart disease in men and women. METHODS AND RESULTS The associations between smoking, serum lipids, blood pressure, and myocardial infarction were examined in a population-based prospective study of 11,843 men and women aged 35 to 52 years at entry. During 12 years, 495 cases of first myocardial infarction among men and 103 cases among women were identified. Myocardial infarction incidence was 4.6 times higher among men. The incidence was increased sixfold in women and threefold in men who smoked at least 20 cigarettes per day compared with never-smokers, and the rate in female heavy smokers exceeded that of never-smoking men. Multivariate analysis identified current smoking as a stronger risk factor in women (relative risk, 3.3; 95% confidence interval [CI], 2.1 to 5.1) than in men (relative risk, 1.9; 95% CI, 1.6 to 2.3). Among those under 45 years old at entry, the smoking-related sex difference was more pronounced (in women: relative risk, 7.1; 95% CI, 2.6 to 19.1) (in men: relative risk, 2.3; 95% CI, 1.6 to 3.2). Serum total cholesterol, HDL cholesterol, and systolic blood pressure were also highly significant predictors in both sexes. CONCLUSIONS Smoking was a stronger risk factor for myocardial infarction in middle-aged women than in men. Relative risks associated with serum lipids and blood pressure were similar despite large sex differences in myocardial infarction incidence rates.

Carotid Atherosclerosis Is a Stronger Predictor of Myocardial Infarction in Women Than in Men: A 6-Year Follow-Up Study of 6226 Persons: The Tromsø Study

Background and Purpose— Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI). Methods— IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered. Results— During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a higher MI risk with more echolucent plaque. The adjusted RR (95% CI) in the highest versus lowest IMT quartile was 1.73 (0.98 to 3.06) in men and 2.86 (1.07 to 7.65) in women. When we excluded bulb IMT from analyses, IMT did not predict MI in either sex. Conclusions— In a general population, carotid plaque area was a stronger predictor of first-ever MI than was IMT. Carotid atherosclerosis was a stronger risk factor for MI in women than in men. In women, the risk of MI increased with plaque echolucency.

Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12

CONTEXT Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk. OBJECTIVE To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials. DESIGN, SETTING, AND PARTICIPANTS Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007. INTERVENTIONS Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721). MAIN OUTCOME MEASURES Cancer incidence, cancer mortality, and all-cause mortality. RESULTS During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B(12) vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B(12) vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B(12) vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12). Vitamin B(6) treatment was not associated with any significant effects. CONCLUSION Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00671346.

Cohort Profile: Cohort of Norway (CONOR)

A number of large population-based cardiovascular surveys have been conducted in Norway since the beginning of the 1970s. The surveys were carried out by the National Health Screening Service in cooperation with the universities and local health authorities. All surveys comprised a common set of questions, standardized anthropometric and blood pressure measurements and non-fasting blood samples that were analysed for serum lipids at the Ulleval Hospital Laboratory. These surveys provided considerable experience in conducting large-scale population-based surveys, thus an important background for the Cohort of Norway (CONOR). In the late 1980s the Research Council of Norway established a programme in epidemiology. This also gave stimulus to the idea of establishing a cohort including both core survey data and stored blood samples. In the early 1990s, all universities, the National Health Screening Service, The National Institute of Public Health and the Cancer Registry discussed the possibility of a national representative cohort. The issue of storing blood samples for future analyses raised some concern and it was discussed in the parliament. In 1994, the Ministry of Health appointed the Steering Committee for the CONOR collaboration. In 1994–95, the fourth round of the Tromso Study was conducted, and became the first survey to provide data and blood samples for CONOR. During the years 1994–2003, a number of health surveys that were carried out in other counties and cities also provided similar data for the network. So far, 10 different surveys have provided data and blood samples for CONOR (Figure 1). The administrative responsibility for CONOR was given to the Norwegian Institute of Public Health (NIPH) in 2002. The CONOR collaboration is currently a research collaboration between the NIPH and the Universities of Bergen, Oslo, Tromso and Trondheim.

Association between heart rate and atherogenic blood lipid fractions in a population. The Tromsø Study.

BackgroundProspective epidemiological studies indicate that elevated heart rate may carry increased risk for coronary heart disease. Little is known about the relation between heart rate and serum lipid and lipoprotein concentrations in the general population. Methods and ResultsWe assessed anthropometric and life-style determinants of heart rate and examined the association between heart rate and serum lipid and lipoprotein concentrations in a cross-sectional study of 9,719 men and 9,433 women 12–59 years old. Stratified and multivariate analyses were used to detect possible modification of effect and to control for confounding variables. Heart rate was positively associated with male sex and smoking, decreased with body height and physical activity, and showed a U-shaped relation to body mass index. In both sexes, there was a significant progressive increase in age-adjusted levels of total cholesterol, non–high density lipoprotein (HDL) cholesterol, and triglycerides and a decrease in HDL cholesterol with heart rate. Men with heart rate > 89 beats per minute had 14.5% higher non-HDL cholesterol and 36.3% higher triglyceride levels than men with heart rate < 60 beats per minute. The corresponding differences in women were 12.5% and 22.2%. The associations remained significant when anthropometric and life-style factors were controlled for. The slopes relating total and non-HDL cholesterol level to heart rate were steeper with advancing age. ConclusionsIncreases in heart rate correlate with higher levels of atherogenic serum lipid fractions in the general population. Alterations in aortic impedance and/or autonomic influences may underlie these associations.

Body Height, Cardiovascular Risk Factors, and Risk of Stroke in Middle-aged Men and Women A 14-Year Follow-up of the Finnmark Study

BACKGROUND Geographical differences in stroke mortality are not fully explained by population variations in blood pressure and antihypertensive treatment. Some studies have suggested that factors connected with health and nutrition in early life may be related to stroke morbidity and mortality. Body height is a sensitive marker for socioeconomic conditions, but results are conflicting as to whether height is associated with stroke. METHODS AND RESULTS In a population-based study, we investigated stroke incidence in relation to height and classic cardiovascular risk factors. A total of 13,266 men and women 35 to 52 years of age were followed for 14 years, and 241 first events of stroke were registered. Stroke incidence was 36% higher in men. Height was inversely related to stroke in a dose-response manner. Per 5-cm increase in height, the age-adjusted risk of stroke was 25% lower in women (P < .0001) and 18% lower in men (P = .0007). Systolic blood pressure and daily smoking were positively associated with stroke in both sexes, while serum triglyceride level was a significant risk factor in women only (relative risk per 1 mmol/L, 1.3; 95% CI, 1.1 to 1.5). The associations remained after adjustment for possible confounders and were also observed in certain subtypes of stroke. CONCLUSIONS The results are consistent with the theory that factors influencing early growth as well as adult lifestyle factors contribute to cerebrovascular disease in adult age.

The Tromsø Heart Study: distribution of, and determinants for, gamma-glutamyltransferase in a free-living population.

Gamma-glutamyltransferase (GGT) was measured in 1579 men, aged 20-54 years, and 1654 women, aged 20-49 years, screened for coronary risk factors. The distribution was right-skewed with medians 15 and 10 U/l for men and women, respectively. Less than 3.8% of the men and 0.8% of the women had GGT greater than or equal to 50 U/l. The low level of GGT matched well with the low mortality of cirrhosis and the modest use of alcohol in Norway. Multiple regression analysis for each sex showed a strong positive association with body mass index, use of alcohol and, unexpectedly, a negative association with coffee consumption, whereas serum triglycerides and the time since the last meal showed a weaker positive association. In women, use of oral contraceptives was positively associated with GGT.