Predictiveness of body mass index for fatal coronary heart disease in men according to length of follow-up: a 21-year prospective cohort study.

AIMS: To test the association between body mass index (BMI) and other coronary risk factors and the risk of a fatal coronary heart disease (CHD) event in different time periods during follow-up. METHODS: Prospective cohort study with a 21 year follow-up period. A screened sample of 14,403 men aged 40-49 years initially free of CHD. Risk of fatal CHD was calculated for 21 years' cumulative follow-up and for four consecutive 5-year periods. RESULTS: After adjustment for age and the other risk factors, total cholesterol and systolic blood pressure retained their predictive strength for CHD mortality throughout follow-up. Though cigarette smoking remained a significant predictor, the relative risk decreased with time (test of trend: p=0.01). Intermediate to vigorous physical activity at leisure was protective for 10 years of follow-up and a question on mental stress for 5 years. The test of trend indicated that the risk associated with BMI increased with the duration of follow-up (p=0.002). CONCLUSIONS: Our data show that coronary risk factors predicted CHD mortality differently according to the length of follow-up, and suggest that the harm associated with obesity may take more than a decade to become evident, in contrast to the classical CHD risk factors.

Risk-factor profile for the incidence of subarachnoid and intracerebral haemorrhage, cerebral infarction, and unspecified stroke during 21 years' follow-up in men.

AIMS: To study the risk-factor profile for the incidence of non-fatal and fatal stroke among middle-aged men according to the stroke subtypes subarachnoid or intracerebral haemorrhage, cerebral infarction, and unspecified stroke. METHODS: The study design is a prospective cohort study. A total of 16,209 men aged 40-49 years resident in Oslo were screened for cardiovascular disease risk factors in 1972-73. Of these, 14,403 men had no cardiovascular symptoms or diseases or diabetes. The incidence of stroke after 21 years of follow-up of all men was extracted from hospital records and linkage to Statistics Norway. RESULTS: A total of 429 non-fatal and 107 fatal stroke events were registered. Case fatality within 28 days (number and percentage of cases) was 51% (41, 7.7%) for subarachnoid haemorrhage, 39% (67, 12.6%) for cerebral haemorrhage, 10% (246, 46.3%) for cerebral infarct, and 19% (177, 33.4%) for unspecified stroke. Risk of stroke (not subarachnoid haemorrhage) increased with the presence of symptoms or a history of cardiovascular disease or diabetes. In multivariate analysis of men without CVD or diabetes, high blood pressure was a risk factor for all subtypes of stroke; furthermore, daily smoking was a risk factor for all subtypes except subarachnoid haemorrhage. Serum cholesterol and glucose concentrations and height (inverse association) were independently associated with cerebral infarction. Smoking was a significantly stronger predictor of fatal than non-fatal events. CONCLUSIONS: The risk-factor profile differed according to the underlying subtype of stroke. Cerebral infarction clearly shared with myocardial infarction the classical risk factors, including non-fasting glucose concentration.

Effect of diet or very long chain omega-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elderly men with hypercholesterolaemia.

BACKGROUND: This randomized study targeted a comparison of the effect of 3-year diet counselling or omega-3 polyunsaturated fatty acid (PUFA) supplementation (2.4 g/day) on the progression of atherosclerosis in carotid arteries and on finger pulse wave propagation. METHODS: Measurements were assessed by high-resolution B-mode ultrasound and a photopletysmographic finger pulse-sensor, respectively. Altogether, 563 elderly men with long-standing hyperlipidaemia were randomized into four groups: controls (no dietary counselling and placebo); dietary counselling (and placebo); omega-3 PUFA supplementation (no dietary counselling); dietary counselling and omega-3 PUFA supplementation. RESULTS: In the diet only group, the carotid intima-media thickness increase (0.929 to 0.967 mm) was significantly less than in the control group (0.909 to 0.977 mm), (P = 0.018). Significant increase in carotid plaques score and plaques area were observed in all four groups, but without between group differences. Changes in carotid intima-media thickness and in high-density lipoprotein-cholesterol were negatively correlated (adjusted P < 0.001). Pulse wave propagation time decreased significantly in the control group (206 to 198 ms; P = 0.002), reflecting reduced arterial elasticity. In the group receiving omega-3 PUFA only, pulse wave propagation time increased significantly when compared with the control group (P = 0.013). CONCLUSION: Reduced progression in carotid intima-media thickness was observed after dietary counselling, whereas omega-3 PUFA supplementation imposed a favourable effect on arterial elasticity.

Influence of long-term intervention with dietary counseling, long-chain n-3 fatty acid supplements, or both on circulating markers of endothelial activation in men with long-standing hyperlipidemia.

BACKGROUND: Dietary factors and very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may influence the atherothrombotic process. Elevated concentrations of circulating cell adhesion molecules, thrombomodulin (TM), von Willebrand factor (vWF), and tissue-type plasminogen activator antigen (tPAag) are related to atherothrombotic cardiovascular disease. OBJECTIVE: The randomized Diet and Omega-3 Intervention Trial (DOIT) targeted a comparison of the effect of 3-y dietary counseling, n-3 PUFA supplementation (2.4 g/d), or both on circulating markers of endothelial activation. DESIGN: The study included 563 elderly men with long-standing hyperlipidemia. The men were randomly assigned by factorial design into 4 groups: control (no dietary counseling and placebo capsules), dietary counseling (and placebo capsules), n-3 PUFA supplementation (no dietary counseling), and dietary counseling and n-3 PUFA supplementation. RESULTS: Serum concentrations of fatty acids reflected good compliance. Dietary counseling was followed by significantly reduced concentrations of soluble intercellular adhesion molecule 1 (sICAM-1; P < 0.001), sTM (P = 0.004), and tPAag (P < 0.001) than in subjects without dietary counseling. After n-3 PUFA supplementation, significantly reduced concentrations of sICAM-1 (P < 0.001) and sTM (P = 0.006) were observed when compared with subjects receiving placebo capsules. An increase in tPAag was not significantly different from that observed in subjects receiving placebo capsules. For sICAM-1, a significant effect was observed for both interventions combined. CONCLUSIONS: Each intervention (dietary counseling or n-3 PUFA supplements) reduced sTM and sICAM-1 concentrations, indicating decreased endothelial activation. The tPAag increase in the groups not receiving dietary counseling (pooled), which indicates progression of atherosclerosis, was significantly counteracted by dietary counseling.

Fluvastatin and lifestyle modification for reduction of carotid intima-media thickness and left ventricular mass progression in drug-treated hypertensives.

OBJECTIVES: The Hypertension High Risk Management trial (HYRIM) investigated the effect of fluvastatin treatment and lifestyle intervention on development of carotid intima-media thickness (IMT) in drug-treated hypertensive patients. METHODS AND RESULTS: HYRIM was a placebo-controlled, 2 x 2 factorial trial in which 568 drug-treated hypertensive men aged 40-74 years with total cholesterol 4.5-8.0 mmol/L, triglycerides <4.5 mmol/L, body mass index 25-35 kg/m2, and a sedentary lifestyle were randomized to receive either fluvastatin, 40 mg daily, or placebo, and either intensive lifestyle intervention (physical activity and diet) or usual care (treatment of hypertension and other disorders by own private physician). Carotid IMT was assessed by B-mode ultrasound vasculography and left ventricular (LV) mass was calculated from ultrasound recordings of the heart. Fluvastatin alone reduced the primary study endpoint of 4-year development of IMT in the common carotid artery (CCA) compared with placebo (p=0.0297). Carotid bulb IMT progression over 4 years was also significantly (p=0.0214) reduced by fluvastatin compared with placebo. Fluvastatin significantly lowered LDL-C levels (mean net difference through 4 years, 0.6 mmol/L; p<0.0001), and reduced the 2-year development of LV mass (p=0.0144) compared with placebo. Lifestyle intervention had no significant effect on LDL-C, carotid IMT or LV mass, and did not increase the effects of fluvastatin. CONCLUSIONS: In drug-treated hypertensive patients in a usual care setting, fluvastatin treatment reduces progression of carotid IMT and LV mass.

[Cardiovascular risk factors among 40-year old men and women in Oslo 1981-1999]. / Risikofaktorer for hjerte- og karsykdom blant 40-åringer i Oslo 1981-99.

BACKGROUND: Between 1981 and 1991, the City of Oslo offered all its 40-year-old citizens screening for risk factors for cardiovascular disease. We describe changes in risk factors over this period. MATERIAL AND METHODS: Between 1981 and 1999, a total of 104,482 men and women born between 1941 and 1959 were invited to undergo screening. RESULTS: The attendance rate was slightly above 55% in the initial years when the City of Oslo had a centralised administration. After a decentralisation to 25 city districts in 1988, attendance dropped considerably. Body weight, triglycerides, physical inactivity, prevalence of metabolic syndrome and diabetes all increased over the period. The classic risk factors, including total serum cholesterol, high blood pressure and cigarette smoking, were all gradually reduced. INTERPRETATION: With regard to the classic risk factors, the findings are consistent with other investigations. The increase in body weight and some other characteristics of the metabolic syndrome are causes for concern.

Trends in the incidence of acute myocardial infarction and stroke: a 21-year follow-up of the Oslo study.

OBJECTIVES: To explore changes in the incidence of fatal and nonfatal myocardial infarction (MI) and stroke in the same male population over two decades. DESIGN: Men aged 40-49 born in the years 1923-1932 (N= 16,209) resident in Oslo participated in a cardiovascular screening programme in 1972-1973. Nonfatal cases of MI and stroke were obtained from hospital records and causes of death were ascertained by linkage to Statistics Norway. The closing date was December 31, 1993. RESULTS: The cohort had a lower mortality rate than the general Norwegian population. First nonfatal and fatal MIs declined in each age and birth cohort during the entire follow-up. The incidence of nonfatal and fatal stroke decreased about 10 years after the initial screening. The risk of men with Rose questionnaire-based symptoms of angina or claudication was between that of healthy men and men with established cardiovascular disease or diabetes. CONCLUSIONS: There has been a reduction in both nonfatal and fatal incident cases of MI and stroke 10 years later indicating a pronounced change in all age groups and a lasting change throughout the period of follow-up. The Rose questionnaire predicted both future stroke and MI.

Urban air pollution and mortality in a cohort of Norwegian men.

We investigated the association between total and cause-specific mortality and individual measures of long-term air pollution exposure in a cohort of Norwegian men followed from 1972-1973 through 1998. Data from a follow-up study on cardiovascular risk factors among 16,209 men 40-49 years of age living in Oslo, Norway, in 1972-1973 were linked with data from the Norwegian Death Register and with estimates of average yearly air pollution levels at the participants' home addresses from 1974 to 1998. Cox proportional-hazards regression was used to estimate associations between exposure and total and cause-specific mortality. During the follow-up time 4,227 men died from a disease corresponding to an ICD-9 (International Classification of Diseases, Revision 9) code < 800. Controlling for a number of potential confounders, the adjusted risk ratio for dying was 1.08 [95% confidence interval (CI), 1.06-1.11] for a 10- microg/m3 increase in average exposure to nitrogen oxides (NOx) at the home address from 1974 through 1978. Corresponding adjusted risk ratios for dying from a respiratory disease other than lung cancer were 1.16 (95% CI, 1.06-1.26); from lung cancer, 1.11 (95% CI, 1.03-1.19); from ischemic heart diseases, 1.08 (95% CI, 1.03-1.12); and from cerebrovascular diseases, 1.04 (95% CI, 0.94-1.15). The findings indicate that urban air pollution may increase the risk of dying. The effect seemed to be strongest for deaths from respiratory diseases other than lung cancer.

[How to identify individuals with elevated cardiovascular risk?]. / Hvordan identifisere personer med høy risiko for kardiovaskulaer sykdom?

In spite of a substantial decline in the morbidity and the mortality from coronary heart disease in Norway since 1970-1975, cardiovascular disease remains the leading cause of death. The prevention of premature cardiovascular disease includes a mass strategy as well an individual strategy. While the first aims at changing life habits in the whole population, the latter is directed towards individuals with elevated cardiovascular risk. Non-pharmacological and pharmacological modes of treatment have been demonstrated to be effective in reducing cardiovascular events. However, the value of such measures depends on our ability to identify high-risk individuals. This paper describes different approaches in preventive medicine, from population screening to the screening of relatives of patients with premature disease. While doctors previously focused on whether blood pressure or cholesterol levels were above the defined limits, a global risk assessment is now recommended. Information regarding family history, smoking and exercise habits, lipid values, blood pressure, and the presence of diabetes must be obtained in a proper risk assessment. In some individuals with intermediate risk, additionally non-invasive tests may be of value in order to ensure that sufficient information has been obtained for a recommendation of preventive measures.

Dietary and antismoking advice and ischemic heart disease mortality in men with normal or high fasting triacylglycerol concentrations: a 23-y follow-up study.

BACKGROUND: In the Oslo Diet and Antismoking Trial, 1232 high-risk men aged 40-49 y were randomly assigned to either a lifestyle intervention group or a control group for 5 y. The study showed a significant reduction in ischemic heart disease (IHD) events in the intervention group. OBJECTIVE: Our objective was to examine this cohort 23 y after the start of the trial. DESIGN: We examined the effect of group assignment on IHD mortality in subjects with a normal (below the median; range: 0.69-2.00 mmol/L; n = 615) or a high (at or above the median; range: 2.01-13.80 mmol/L; n = 617) fasting triacylglycerol concentration in 1972-1973 (at inclusion into the study). We recorded vital status on 31 December 1996 and ascertained causes of death by linkage to Statistics Norway. RESULTS: In the men with a high triacylglycerol concentration, IHD death occurred in 25 (8.13%) subjects in the intervention group and in 44 (14.2%) subjects in the control group (relative risk: 0.57; 95% CI: 0.36, 0.91; P = 0.02). An adjusted Cox proportional hazards model yielded a hazard ratio of 0.56 (95% CI: 0.34, 0.93; P = 0.027). In the men with a normal triacylglycerol concentration, the intervention had no detectable effect on IHD mortality (adjusted hazard ratio: 1.10; 95% CI: 0.66, 1.83; P = 0.7). CONCLUSIONS: These data suggest that advice to change diet and smoking habits reduced the relative risk of IHD mortality after 23 y in men with high triacylglycerol concentrations. Men with normal triacylglycerol concentrations did not appear to achieve this long-term benefit of lifestyle intervention.

A high risk score for coronary heart disease is associated with the metabolic syndrome in 40-year-old men and women.

OBJECTIVE: Guidelines recommend follow-up of people whose 10-year risk of coronary heart disease (CHD) is > 10%. We calculated CHD risk, number of risk factors and occurrence of the metabolic syndrome among screened 40-year-old men and women. DESIGN: A total of 1547 women and 1374 men participated in a cardiovascular risk factor screening programme in 1997-1999 in Oslo. Of 387 (13%) recalled for further examination and advice, 337 (87%) attended. We used the National Cholesterol Education Program criteria to define the metabolic syndrome and the Framingham risk score to assess absolute 10-year risk of CHD and counted nine risk factors (male, southeast-Asian origin, low education, smoking, premature familial cardiovascular disease (CVD), hypertension, high waist circumference, impaired fasting glucose or diabetes and high apolipoprotein B). RESULTS: More than one-third of subjects recalled for hypertension (n = 88) or low high-density lipoprotein (HDL) cholesterol (n = 95) had the metabolic syndrome. Of 55 subjects with a 10-year risk score > 10%, 33 (60%) had the metabolic syndrome. Subjects with the metabolic syndrome had a higher risk score compared with their counterparts (P < 0.001); among men with the metabolic syndrome, the mean +/- SD risk score was 10.0 +/- 4.4%. Subjects with dyslipidaemia [high triglyceride and normal low-density lipoprotein (LDL) cholesterol levels] or combined hyperlipidaemia had a higher risk score and more risk factors compared with subjects with isolated high LDL cholesterol (P < 0.05). Only 12% of subjects with hypertension were taking drugs and of 237 subjects with a lipid disorder, 30% had been given dietary advice and one was taking a lipid-lowering drug. CONCLUSION: CVD screening should focus on identifying people with features of the metabolic syndrome in this age group. The screening programme uncovered a substantial potential for CVD prevention.

Improved fibrinolysis after 1-year treatment with HMG CoA reductase inhibitors in patients with coronary heart disease.

The study was aimed to investigate the effect of two different statins on the levels of haemostatic variables reflecting procoagulant and fibrinolytic activity in patients with coronary heart disease (CHD), with the hypothesis that statins might beneficially modify these levels. Fifty-eight patients were randomized to treatment with atorvastatin (n=28) or simvastatin (n=30) for 1 year. The starting dose in both groups was 20 mg/day. Fasting blood samples were collected before and after 12-month treatment for determinations of fibrinogen, prothrombin fragment 1+2 (F1+2), plasma D-dimer, soluble tissue factor, tissue plasminogen activator (tPA) antigen, tPA activity, plasminogen activator inhibitor type-1 activity (PAI-1 activity) and serum D-dimer as a global test of fibrinolytic activity. In the total population, improved fibrinolytic activity was observed after 1 year with increased levels of serum D-dimer (P=.001) and tPA activity (P=.024) and a reduction in tPA antigen (P=.048). No statistically significant changes were observed in any of the measured coagulation variables. Separately examined, an improved fibrinolytic profile was seen in the atorvastatin group with a significant increase in serum D-dimer (P=.005), a borderline increase in tPA activity (P=.083) and a borderline reduction in tPA antigen (P=.069). Within the simvastatin group, a reduction in prothrombin F1+2 was observed (P=.038). The differences in changes between the groups were statistically significant only for global fibrinolysis (serum D-dimer, P=.046). In conclusion, an improved fibrinolytic profile was observed after statin treatment, most pronounced with atorvastatin. The results indicate that the drugs promote a profibrinolytic profile, and may in part explain the benefit of statin treatment rendered in the prevention of CHD.

Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease.

The study was aimed at investigating the effects, after treatment for 1 year, of two different statins on the levels of circulating biochemical markers of endothelial function in patients with established coronary heart disease, with the hypothesis that statins might reduce these levels. Twenty-eight patients were randomized to treatment with atorvastatin and 30 to simvastatin for 1 year. The starting dose in both groups was 20 mg/day. Soluble forms of P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined to assess inflammatory activity of the endothelium, and tissue plasminogen activator antigen (tPAag), von Willebrand factor and thrombomodulin for evaluation of the haemostatic function. In the total study population there were significantly reduced levels after 1 year treatment in ICAM-1 (P<0.001), E-selectin (P=0.022) and P-selectin (P<0.001), whereas a significant increase was observed in VCAM-1 (P=0.003). Almost the same pattern was seen within both groups although the increase in VCAM-1 was only seen in the simvastatin group (P=0.017). An overall reduction in tPAag was further observed (P=0.048). The reduction in proinflammatory and to some extent haemostatic markers of endothelial function after 1 year treatment with either simvastatin or atorvastatin may be indicative of a less activated state of the endothelium which possibly may contribute to modulation of the progression of atherosclerosis.