Cardiovascular risk factors in the Northern Sweden MONICA Study

In the WHO MONICA Study, determinants and trends in cardiovascular disease are monitored during a 10-year period in 40 centers in 27 countries. The Northern Sweden MONICA Center is located furthest to the north of all participating centers. In this report, baseline data on cardiovascular risk factors are presented. In the first population screening, 1,625 of 2,000 (81%) invited individuals participated. Diastolic blood pressure greater than or equal to 90 mmHg was recorded in 19% and 9% were on drug treatment for hypertension. Median cholesterol level was 6.10 mmol/l and the frequency of hypercholesterolemia was high. A body mass index of greater than or equal to 30, indicating severe obesity, was observed in 9%, a lower proportion than in most other European populations. Among men, the total proportion of tobacco consumers was 49%, including 22% snuffers. Of the women, 31% were tobacco consumers, very few being snuffers. Women had, in general, a more favorable cardiovascular risk factor profile up to the age of 45. Thereafter, the two genders were similar. By international comparisons, the population in northern Sweden is characterized by high serum cholesterol levels, intermediate blood pressure levels, a relatively low prevalence of severe obesity and a high consumption of smokeless tobacco.     

Homozygosity for the C677-->T mutation of 5,10-methylenetetrahydrofolate reductase and total plasma homocyst(e) ine are not associated with greater than normal risk of a first myocardial infarction in northern Sweden

BACKGROUND: Results of several case-control studies have shown elevated total plasma homocyst(e)ine (TPH) and homozygosity for the point mutation C677-->T in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) to be associated with a greater than normal risk of atherosclerotic vascular disease. However, there have been few epidemiologic studies and the interpretation of the results is not clear-cut. OBJECTIVE: To elucidate whether homozygosity for the point mutation C677-->T in the gene for MTHFR, and TPH are risk factors for a first myocardial infarction. DESIGN: A prospective nested case-control study in Northern Sweden. METHODS: Among more than 36000 persons screened, 78 cases satisfied the inclusion criterion of having developed, after sampling, a first myocardial infarction. For each case, two controls matched for sex and age were randomly selected. RESULTS: We found no statistically significant difference among the prevalences of the three possible MTHFR genotypes -/- (no mutation), +/+ (both alleles have the mutation), and +/- among cases and controls in univariate conditional logistic regression analysis. Mean levels of TPH in patients and controls were 12.2+/-4.9 and 12.2+/-3.5 micromol/l (means +/- SD), respectively (NS). CONCLUSIONS: In this study neither homozygosity for the point mutation C677-->T in the gene for MTHFR nor TPH was related to a greater than normal risk of a first myocardial infarction for members of the population of northern Sweden. Further research is needed in order to show whether TPH is an independent risk factor for a first myocardial infarction.     

Coronary risk factors, diet and vitamins as possible explanatory factors of the Swedish north-south gradient in coronary disease: a comparison between two MONICA centres

Abstract. Rosengren A, Stegmayr B, Johansson I, Huhtasaari F, Wilhelmsen L (Sahlgrenska University Hospital/Östra, Göteborg, Umeå University Hospital and Umeå University, Umeå and Luleå Hospital, Luleå, Sweden). Coronary risk factors, diet and vitamins as possible explanatory factors of the Swedish north–south gradient in coronary disease: a comparison between two MONICA centres. J Intern Med 1999; 246: 577–586. Objective. To investigate whether differences in serum lipids, diet, plasma vitamins or other risk factors explain the higher incidence of cardiovascular disease in the northern parts of Sweden, compared to Göteborg on the west coast. Design. A comparison between the two Swedish MONICA populations in northern Sweden (NSW) and in Göteborg (GOT) in 1990. Setting. Norrbotten and Västerbotten counties in the north of Sweden and the city of Göteborg on the west coast. Subjects. In the north 1583 men and women aged 25–64 years were investigated, and in Göteborg 1574 men and women. Plasma vitamins were examined in a subsample of men aged 40–49 (n = 259). Main outcome measures. Serum lipids, blood pressure, anthropometric measurements, smoking habits, physical activity, diet, education, and plasma vitamins. Results. NSW men and women had mean serum total cholesterol of 6.30 (standard deviation 1.23) mmol L^–1 and 6.12 (1.33) mmol L^–1, compared to 5.75 (1.14) mmol L^–1 and 5.67 (1.24) mmol L^–1 in GOT men and women (P = 0.0001). NSW men and women were shorter and had higher body mass index than in Göteborg. Cigarette smoking was slightly more prevalent amongst GOT men and women. Göteborg men and women more often had more than compulsory school education, compared to NSW men and women, whereas there were no differences in physical activity during leisure time. There were no differences in vegetable consumption, whereas fruit was consumed more frequently by NSW women compared to GOT women, with a higher intake of fibre and ascorbate. Consumption of wine and total alcohol consumption were higher in Göteborg, whereas NSW men and women drank significantly more coffee. In the subsample of men (aged 40–49) who had plasma vitamins measured, men in Göteborg had slightly higher mean retinol concentrations (P = 0.005) and lutein and zeaxanthine levels (P = 0.006 and 0.009, respectively) compared to northern men, but there were no differences with respect to α- or β-carotene, ascorbic acid or lipid-adjusted vitamin E. NSW men had slightly higher plasma iron and magnesium concentrations (P = 0.005 and 0.001, respectively). Conclusion. The largest and most consistent differences between Göteborg and northern Sweden were found for serum cholesterol, probably reflecting differences in intake of saturated fat. The differences in serum cholesterol may explain a substantial part of the differences in coronary heart disease morbidity and mortality. We found no consistent differences concerning vegetable and fruit consumption. More alcohol was consumed in Göteborg. Differences in education and childhood conditions, as reflected in differences in height, may contribute to the north–south gradient with respect to CHD incidence and mortality.     

Marked improvement in survival after acute myocardial infarction in middle-aged men but not in women. The Northern Sweden MONICA study 1985-94

OBJECTIVES: The aim of this study was to analyse time trends in survival after acute myocardial infarction with special emphasis on sex differences. DESIGN: Within the framework of the population-based WHO MONICA Project, all acute myocardial infarction events were recorded in the age group 25-64 years in northern Sweden during the period 1985-94. All first-ever myocardial infarction patients were followed for information on vital status. SUBJECTS: A total of 3397 men and 860 women with acute myocardial infarction, during the period between 1985 and 1994. MAIN OUTCOME MEASURES: Case fatality rates after first-ever acute myocardial infarction. RESULTS: When compared with the 1985-86 cohort, the age-adjusted odds ratio for death within 1 year after acute myocardial infarction was 0.59 (95% CI 0.46-0.76) in the 1993-94 male cohort but 0.99 (95% CI 0.61-1.60) in the female 1993-94 cohort. Corresponding age-adjusted proportions of death within 1 year were 33.3% and 22.9% in men and 27.5% and 27.3% in women in 1985-86 and 1993-94, respectively. The odds ratio for 3-year case fatality amongst those who survived the first 28 days was 0.34 (95% CI 0.21-0.55) in 1991-92 compared with 1985-86 in men and 0.91 (0.43-1.94) in women. CONCLUSION: Both short- and long-term survival after AMI have improved markedly in men over the last decade. There is a disturbing sex difference in that, during the same period, survival in women with AMI has not improved at all. This sex difference was not explained by differences in conventional prognostic factors.     

Lipoprotein(a) and cholesterol levels act synergistically and apolipoprotein A-I is protective for the incidence of primary acute myocardial infarction in middle-aged males. An incident case–control study from Sweden

Abstract. Dahlén GH, Weinehall L, Stenlund H, Jansson J-H, Hallmans G, Huhtasaari F, Wall S (Umeå University, Umeå; Skellefteå County Hospital; and Luleå-Boden County Hospital, Sweden). Lipoprotein(a) and cholesterol levels act synergistically and apolipoprotein A-I is protective for the incidence of primary acute myocardial infarction in middle-aged males. An incident case–control study from Sweden. J Intern Med 1998; 244 : 425–30.

Objective

To further establish the importance of total plasma apolipoprotein A-I and lipoprotein(a) in the prediction of primary acute myocardial infarction (AMI) in men.

Design

An incident case–control study.

Setting

The study was nested within the Västerbotten Intervention Program (VIP) and the Northern Sweden MONICA cohorts.

Subjects

A total of 62 male AMI cases and 124 matched controls, randomly selected from the study cohorts.

Results

In multivariate logistic regression, significant odds ratios (OR) were found for Lp(a) above 200 mg L^?1, apo A-I below the mean value (1136 mg L^?1) and total cholesterol (TC) above 7.8 mmol L^?1. TC interacted significantly with Lp(a); for Lp(a) above 200 mg L^?1 and TC below 6.5 mmol L^?1, OR = 5.6; for Lp(a) above 200 mg L^?1 and TC above 6.5 mmol L^?1, OR = 12.6. To evaluate the potential effect of reducing high levels of Lp(a) or TC on the incidence of AMI in males, the attributable risk percentage (ARP) was calculated when interaction between the two variables was present. ARP is 31% for Lp(a) and 21% for TC, implying that 31% of the cases are due to high Lp(a) and 21% of the cases are due to high TC levels.

Conclusions

In the Swedish male population, total apo A-I in plasma is a protective factor and a plasma Lp(a) level above 200 mg L^?1 is a risk factor for AMI in males. A TC level above 6.5 mmol L^?1 increased the risk of AMI if the Lp(a) level was above 200 mg L^?1, suggesting Lp(a) to be useful in identifying high risk individuals needed to be treated.

     

Smokeless tobacco as a possible risk factor for myocardial infarction: a population-based study in middle-aged men

OBJECTIVES: To explore whether the use of snuff affects the risk of myocardial infarction (MI). BACKGROUND: Snuff and other forms of smokeless tobacco are widely used in some populations. Possible health hazards associated with the use of smokeless tobacco remain controversial. METHODS: In a population-based study within the framework of the Northern Sweden center of the World Health Organization Multinational Monitoring of Trend and Determinants in Cardiovascular Disease (WHO MONICA) Project, tobacco habits were compared in 25- to 64-year-old men with first-time fatal or nonfatal MI and referent subjects matched for age and place of living (687 cases, 687 referents). RESULTS: The unadjusted odds ratio (OR) for MI in regular cigarette smokers as compared with men who never used tobacco was 3.65 (95% confidence interval [CI] 2.67 to 4.99). When nonsmoking regular snuff dippers were compared with never-users of tobacco, the unadjusted OR was 0.96 (0.65 to 1.41). After adjustment for multiple cardiovascular risk factors, the OR was 3.53 (95% CI 2.48 to 5.03) for regular smoking and 0.58 (95% CI 0.35 to 0.94) for regular snuff dipping. Restricting the analyses to fatal cases of myocardial (including sudden death) showed a tendency towards increased risk among snuff dippers 1.50 (95% CI 0.45 to 5.03). CONCLUSIONS: The risk of MI is not increased in snuff dippers. Nicotine is probably not an important contributor to ischemic heart disease in smokers. A possible small or modest detrimental effect of snuff dipping on the risk for sudden death could not be excluded in this study due to a limited number of fatal cases.     

Markers of high fish intake are associated with decreased risk of a first myocardial infarction

High intake of fish has been associated with reduced risk of CHD. The high content of n-3 polyunsaturated fatty acids (PUFA) in fish has been suggested to be a protective factor. In addition, fish is the entirely dominating source of methylmercury for the general population, and the concentration of Hg in erythrocytes (Ery-Hg) is often used as an index of fish consumption. Our aim was to study the relationships between a first-ever myocardial infarction, Ery-Hg, activity of gluthathione peroxidase in erythrocytes (Ery-GSH-Px) and plasma concentration of the n-3 PUFA eicosapentaenoic and docosahexaenoic acids (P-PUFA). In a population-based prospective nested case-control study within Northern Sweden seventy-eight cases of a first-ever myocardial infarction were compared with 156 controls with respect to Ery-Hg, P-PUFA and Ery-GSH-Px. Both Ery-Hg and P-PUFA, but not Ery-GSH-Px, were significantly higher in subjects reporting high fish intake (at least one meal per week) than in those with lower intake. This finding suggests that Ery-Hg and P-PUFA reflect previous long-term fish intake. Low risk of myocardial infarction was associated with high Ery-Hg or high P-PUFA. In a multivariate model the risk of myocardial infarction was further reduced in subjects with both high Ery-Hg and high P-PUFA (odds ratio 0.16, 95 % CI 0.04, 0.65). In conclusion, there is a strong inverse association between the risk of a first myocardial infarction and the biomarkers of fish intake, Ery-Hg and P-PUFA, and this association is independent of traditional risk factors.     

High proinsulin concentration precedes acute myocardial infarction in a nondiabetic population.

Hyperinsulinemia has been shown to have strong and consistent associations with a cluster of cardiovascular risk factors. Yet the associations between hyperinsulinemia and coronary heart disease (CHD) have been weak, at best, and often inconsistent. Most previous studies have analyzed the insulin level using a radioimmunoassay method, which does not separate proinsulin from intact (true) insulin. New methods separating the two have demonstrated that proinsulin may be at least as strongly or even more strongly associated than intact insulin with a CHD-promoting risk factor profile. In this incident case-control study of a nondiabetic population, 67 cases of first acute myocardial infarction (AMI) were compared with 127 individually age- and sex-matched controls. Blood sampling was collected prior to disease outcome. Proinsulin and intact insulin levels were measured using highly sensitive two-site sandwich enzyme-linked immunosorbent assays (ELISAs). The highest quartile of proinsulin, in contrast to intact insulin, showed a greater than threefold increase in AMI compared with the lowest quartile, with an odds ratio (OR) and 95% confidence interval (CI) of 3.5 and 1.2 to 9.9, respectively. The increased risk of AMI persisted after controlling for total cholesterol, smoking status, diastolic blood pressure, and antihypertensive medication, and disappeared after additional control was used for the body mass index. High levels of proinsulin, even in a nondiabetic population, seem to be a strong and independent risk factor for AMI. The mechanism underlying the relationship may be direct via effects on fibrinolysis or, probably more plausibly, indirect, where proinsulin is a marker of an underlying metabolic disturbance.