Aage Tverdal

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project

AIMS The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. METHODS AND RESULTS The project assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 20,5178 persons (88,080 women and 11,7098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total cholesterol/HDL cholesterol ratio. The risk estimations are displayed graphically in simple risk charts. Predictive value of the risk charts was examined by applying them to persons aged 45-64; areas under ROC curves ranged from 0.71 to 0.84. CONCLUSIONS The SCORE risk estimation system offers direct estimation of total fatal cardiovascular risk in a format suited to the constraints of clinical practice.

The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease

The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992-93, when the subjects were aged 40-67 y. In 1997-99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels > 15 micromol/L, but for most conditions, there is a continuous concentration-response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Health consequences of smoking 1–4 cigarettes per day

Objectives: To determine the risk in men and women smoking 1–4 cigarettes per day of dying from specified smoking related diseases and from any cause. Design: Prospective study. Setting: Oslo city and three counties in Norway. Participants: 23 521 men and 19 201 women, aged 35–49 years, screened for cardiovascular disease risk factors in the mid 1970s and followed throughout 2002. Outcomes: Absolute mortality and relative risks adjusted for confounding variables, of dying from ischaemic heart disease, all cancer, lung cancer, and from all causes. Results: Adjusted relative risk (95% confidence interval) in smokers of 1–4 cigarettes per day, with never smokers as reference, of dying from ischaemic heart disease was 2.74 (2.07 to 3.61) in men and 2.94 (1.75 to 4.95) in women. The corresponding figures for all cancer were 1.08 (0.78 to 1.49) and 1.14 (0.84 to 1.55), for lung cancer 2.79 (0.94 to 8.28) and 5.03 (1.81 to 13.98), and for any cause 1.57 (1.33 to 1.85) and 1.47 (1.19 to 1.82). Conclusions: In both sexes, smoking 1–4 cigarettes per day was associated with a significantly higher risk of dying from ischaemic heart disease and from all causes, and from lung cancer in women. Smoking control policymakers and health educators should emphasise more strongly that light smokers also endanger their health.

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.

Body Mass Index in Adolescence in Relation to Cause-specific Mortality: A Follow-up of 230,000 Norwegian Adolescents

The prevalence of obesity in childhood and adolescence has increased worldwide. Long-term effects of adolescent obesity on cause-specific mortality are not well specified. The authors studied 227,000 adolescents (aged 14-19 years) measured (height and weight) in Norwegian health surveys in 1963-1975. During follow-up (8 million person-years), 9,650 deaths were observed. Cox proportional hazards regression was used to compare cause-specific mortality among individuals whose baseline body mass index (BMI) was below the 25th percentile, between the 75th and 84th percentiles, and above the 85th percentile in a US reference population with that of individuals whose BMI was between the 25th and 75th percentiles. Risk of death from endocrine, nutritional, and metabolic diseases and from circulatory system diseases was increased in the two highest BMI categories for both sexes. Relative risks of ischemic heart disease death were 2.9 (95% confidence interval (CI): 2.3, 3.6) for males and 3.7 (95% CI: 2.3, 5.7) for females in the highest BMI category compared with the reference. There was also an increased risk of death from colon cancer (males: 2.1, 95% CI: 1.1, 4.1; females: 2.0, 95% CI: 1.2, 3.5), respiratory system diseases (males: 2.7, 95% CI: 1.4, 5.2; females: 2.5, 95% CI: 1.4, 4.8), and sudden death (males: 2.2, 95% CI: 1.2, 4.3; females: 2.7, 95% CI: 1.1, 6.6). Adolescent obesity was related to increased mortality in middle age from several important causes.

Tea consumption. Relationship to cholesterol, blood pressure, and coronary and total mortality

BACKGROUND AND METHODS The relation of tea to cholesterol, systolic blood pressure, and mortality from coronary heart disease and all causes was studied in 9,856 men and 10,233 women without history of cardiovascular disease or diabetes. All men and women 35-49 years of age from the county of Oppland (Norway) were invited to participate; the attendance rate was 90%. RESULTS Mean serum cholesterol decreased with increasing tea consumption, the linear trend coefficient corresponded to a difference of 0.24 mmol/liter (9.3 mg/dl) in men and 0.15 mmol/liter (5.8 mg/dl) in women between drinkers of less than one cup and those of five or more cups/day, when other risk factors were taken into account. Systolic blood pressure was inversely related to tea with a difference between the same two tea groups of 2.1 mm in men and 3.5 mm in women. Altogether 396 men and 237 women died from all causes, and of these 141 and 18, respectively, died from coronary heart disease during the 12-year follow-up period. The mortality rate was higher (not statistically significant) among persons drinking no tea or less than one cup compared with persons drinking one or more cups/day. This applies to men and women and to coronary heart disease and all-cause mortality. For men, the relative risk (one or more versus less than one cup) for coronary death from Cox regression was 0.64 (95% CI:0.38, 1.07).

Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial.

Randomized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly. Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known. We studied if an intervention with 10 μg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double‐blinded randomized controlled trial. Residents from 51 nursing homes were allocated randomly to receive 5 ml of ordinary cod liver oil (n = 569) or 5 ml of cod liver oil where vitamin D was removed (n = 575). During the study period of 2 years, fractures and deaths were registered, and the principal analysis was performed on the intention‐to‐treat basis. Biochemical markers were measured at baseline and after 1 year in a subsample. Forty‐seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture. The corresponding figures for all nonvertebral fractures were 76 persons (control group) and 69 persons (vitamin D group). There was no difference in the incidence of hip fracture (p = 0.66, log‐rank test), or in the incidence of all nonvertebral fractures (p = 0.60, log‐rank test) in the vitamin D group compared with the control group. Compared with the control group, persons in the vitamin D group increased their serum 25‐hydroxyvitamin D concentration with 22 nmol/liter (p = 0.001). In conclusion, we found that an intervention with 10 μg of vitamin D3 alone produced no fracture‐preventing effect in a nursing home population of frail elderly people.

Obesity in Adolescence and Adulthood and the Risk of Adult Mortality

Background: There are few long-term follow-up data on the relation between body mass index (BMI) in adolescence and in adulthood, and between adolescent BMI and adult mortality. The present study explores these relations. Methods: In Norwegian health surveys during 1963–1999, height and weight were measured for 128,121 persons in a standardized way both in adolescence (age 14–19 years) and 10 or more years later. Persons were followed for an average of 9.7 years after the adult measurement. Cox proportional hazard regression models were used to study the association between adolescent and adult BMI and mortality. Results: The odds ratio of obesity (BMI ≥30) in adulthood increased steadily with BMI in adolescence, from 0.2 for low BMI up to 16 for very high BMI. Very high adolescent BMI was associated with 30–40% higher adult mortality compared with medium BMI. Adjusting for adult BMI explained most of the association of adolescent obesity and mortality, especially among men. Adjustment for smoking did not change the results. Conclusions: Obesity in adolescence tends to persist into adulthood. Adolescent obesity is also connected to excess mortality, but this excess seems to be explained mostly by obesity in adulthood. High BMI in adolescence seems to be predictive of both adult obesity and mortality.

Mortality in relation to smoking history: 13 years' follow-up of 68,000 Norwegian men and women 35–49 years

A total of 44,290 men and 24,535 women aged 35-49 have been followed with respect to different causes of death during 13.3 years on average. A detailed history of smoking, together with other important risk factors, were recorded in a standardized way. Compared with the classical American and British studies, the excess mortality for the smokers was largely the same for the majority of causes. The exceptions were cerebrovascular mortality and suicides and accidents, which were more strongly related to smoking in this study. Furthermore, men who smoked only pipe, had nearly the same coronary heart disease mortality as men who smoked only cigarettes. The same applies to lung cancer mortality. Among men who had quit cigarette smoking, the coronary heart disease mortality decreased with time since quitting to almost the level of the never cigarette smokers after 5 years or more.

Height and body mass index in relation to total mortality

Background. The relation between body mass index (BMI) and mortality is not clear in the literature. An inverse relation between height and mortality has been suggested. We explore these relations in a very large cohort in Norway. Methods. We studied two million men and women, age 20–74 years, who were measured during 1963–2000. These persons were followed for an average of 22.1 years. We used Cox proportional hazard models in the analyses. Also, the optimal BMI (the BMI at the time of measurement that was subsequently related to the lowest mortality) was estimated. Results. Over the study period, 723,000 deaths were registered. The relative risk of death by BMI showed a J- or U-shaped curve, with the lowest rates of death at BMI between 22.5 and 25.0. In men, the optimal BMI increased from 21.6 when measured at age 20–29 to 24.0 when measured at age 70–74. In women, the optimal BMI was consistently higher, increasing from 22.2 to 25.7. Mortality decreased with increased height in men; in women, mortality decreased with height only up to heights of about 160–164 cm and then increased among the tallest women. Conclusions. The relation between BMI and mortality was J- or U-shaped, with the “optimal” BMI varying by age and sex. Height was inversely related to mortality in men and in women up to a height of 165 cm.