Lars Weinehall

General and Abdominal Adiposity and Risk of Death in Europe

BACKGROUND Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001). CONCLUSIONS These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.

High Plasminogen Activator Inhibitor and Tissue Plasminogen Activator Levels in Plasma Precede a First Acute Myocardial Infarction in Both Men and Women Evidence for the Fibrinolytic System as an Independent Primary Risk Factor

BACKGROUND In patients with established ischemic heart disease, prospective cohort studies have indicated that plasminogen activator inhibitor (PAI-1), the inhibitor of the fibrinolytic system, may predict cardiovascular events. So far, there have been no primary prospective studies of PAI-1. METHODS AND RESULTS The aim of the present study was to test whether plasma levels of PAI-1, tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), and thrombomodulin (TM) could predict the occurrence of a first acute myocardial infarction (AMI) in a population with high prevalence of coronary heart disease by use of a prospective nested case-control design. Mass concentrations of PAI-1 and tPA were significantly higher for the 78 subjects who developed a first AMI compared with the 156 references matched for age, sex, and sampling time; for tPA, this increase was independent of smoking habits, body mass index, hypertension, diabetes, cholesterol, and apolipoprotein A-I. The ratio of quartile 4 to 1 for tPA was 5.9 for a patient to develop a first AMI. The association between tPA and AMI was seen in both men and women. Increased levels of vWF were associated with AMI in a univariate analysis. High levels of TM were associated with AMI in women but not in men. CONCLUSIONS The plasma levels of PAI-1, tPA, and vWF are associated with subsequent development of a first AMI; for PAI-1 and tPA, this relation was found in both men and women. For tPA but not for PAI-1 and vWF, this association is independent of established risk factors.

Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort - evaluation of risk factors and their interactions.

The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.

Reduction of selection bias in primary prevention of cardiovascular disease through involvement of primary health care

OBJECTIVE To examine selection bias in social and health factors in a community intervention programme for the prevention of cardiovascular disease by comparing programme data with both census data and a random sample of the same population. DESIGN Cross sectional studies. SETTING All 35 primary health care centres in Västerbotten County, Sweden. SUBJECTS 24,870 individuals who during 1992 and 1993 became 30, 40, 50 or 60 years of age. MAIN OUTCOME MEASURES Total income, socio-economic group, employment, education, body mass index (BMI), total cholesterol, systolic and diastolic blood pressure, and daily smoking. RESULTS The differences in social characteristics between participants and non-participants were marginal, indicating that the social selection bias was small. However, unemployment, low income, and younger age tended to be associated with somewhat lower preference to participate. The overall pattern of health status, as measured by risk factors, was similar rather than dissimilar. While the participants in the intervention health survey had lower mean total cholesterol, their blood pressure was generally higher compared with the reference random sample. CONCLUSIONS The primary health care system in Sweden might serve as a useful base for educational health counselling, at least within a community intervention programme, for all levels of society.

Leptin, but not adiponectin, predicts stroke in males

Objective.  To test whether leptin and adiponectin are risk markers for a first‐ever stroke.

Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project

OBJECTIVE The aim of this study was to compare the quantities of alcohol and types of alcoholic beverages consumed, and the timing of consumption, in centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). These centres, in 10 European countries, are characterised by widely differing drinking habits and frequencies of alcohol-related diseases. METHODS We collected a single standardised 24-hour dietary recall per subject from a random sample of the EPIC cohort (36 900 persons initially and 35 955 after exclusion of subjects under 35 and over 74 years of age). This provided detailed information on the distribution of alcohol consumption during the day in relation to main meals, and was used to determine weekly consumption patterns. The crude and adjusted (by age, day of week and season) means of total ethanol consumption and consumption according to type of beverage were stratified by centre and sex. RESULTS Sex was a strong determinant of drinking patterns in all 10 countries. The highest total alcohol consumption was observed in the Spanish centres (San Sebastian, 41.4 g day-1) for men and in Danish centres (Copenhagen, 20.9 g day-1) for women. The lowest total alcohol intake was in the Swedish centres (Umeå, 10.2 g day-1) in men and in Greek women (3.4 g day-1). Among men, the main contributor to total alcohol intake was wine in Mediterranean countries and beer in the Dutch, German, Swedish and Danish centres. In most centres, the main source of alcohol for women was wine except for Murcia (Spain), where it was beer. Alcohol consumption, particularly by women, increased markedly during the weekend in nearly all centres. The German, Dutch, UK (general population) and Danish centres were characterised by the highest percentages of alcohol consumption outside mealtimes. CONCLUSIONS The large variation in drinking patterns among the EPIC centres provides an opportunity to better understand the relationship between alcohol and alcohol-related diseases.

Abdominal and Gynoid Fat Mass Are Associated with Cardiovascular Risk Factors in Men and Women

CONTEXT Abdominal obesity is an established risk factor for cardiovascular disease (CVD). However, the correlation of dual-energy x-ray absorptiometry (DEXA) measurements of regional fat mass with CVD risk factors has not been completely investigated. OBJECTIVE The aim of this study was to investigate the association of estimated regional fat mass, measured with DEXA and CVD risk factors. DESIGN, SETTING, AND PARTICIPANTS This was a cross-sectional study of 175 men and 417 women. DEXA measurements of regional fat mass were performed on all subjects, who subsequently participated in a community intervention program. MAIN OUTCOME MEASURES Outcome measures included impaired glucose tolerance, hypercholesterolemia, hypertriglyceridemia, and hypertension. RESULTS We began by assessing the associations of the adipose measures with the cardiovascular outcomes. After adjustment for confounders, a sd unit increase in abdominal fat mass was the strongest predictor of most cardiovascular variables in men [odds ratio (OR)=2.63-3.37; P<0.05], whereas the ratio of abdominal to gynoid fat mass was the strongest predictor in women (OR=1.48-2.19; P<0.05). Gynoid fat mass was positively associated with impaired glucose tolerance, hypertriglyceridemia, and hypertension in men (OR=2.07-2.15; P<0.05), whereas the ratio of gynoid to total fat mass showed a negative association with hypertriglyceridemia and hypertension (OR=0.42-0.62; P<0.005). CONCLUSIONS Abdominal fat mass is strongly independently associated with CVD risk factors in the present study. In contrast, gynoid fat mass was positively associated, whereas the ratio of gynoid to total fat mass was negatively associated with risk factors for CVD.

High remaining risk in poorly treated hypertension : the "rule of halves" still exists

Objectives To estimate risk factors for stroke, to examine how different categories of patients with increased blood pressure are associated with risk for first-ever stroke event, and to estimate the proportions of these categories in a geographically defined population in northern Sweden. Setting The study was nested within the Västerbotten Intervention Program and the Northern Sweden MONICA cohorts. Design and participants A population-based cross-sectional study and an incident case–control study were carried out. The incident case–control study comprised 129 cases of first-ever stroke diagnosed during 1985–96, with two randomly selected controls per case, chosen from the same geographically defined population. The cross-sectional study was based on 59 735 participants. Blood pressure status was categorized as: normotensive [systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg]; treated and adequately controlled hypertension (SBP <140 mmHg and DBP <90 mmHg); treated but poorly controlled hypertension (SBP ⩾140 mmHg or DBP ⩾90 mmHg, or both); untreated hypertension (SBP ⩾140 mmHg or DBP ⩾90 mmHg, or both); newly detected increased blood pressure (SBP ⩾140 mmHg or DBP ⩾90 mmHg, or both). Main outcome measure: Risk for first-ever stroke. Results: In the cross-sectional study, 68% of individuals were normotensive, 3% had treated and adequately controlled hypertension, 6% had treated but poorly controlled hypertension, 7% had untreated hypertension, and 16% had newly detected increased blood pressure. In univariate analysis of the case–control study, history of diabetes, daily smoking, obesity, increased blood pressure and the hypertension categories ‘treated but poorly controlled’ and ‘untreated’ were associated with an increased stroke risk. In multivariate logistic regression analysis, only diabetes and the hypertension categories treated but poorly controlled and untreated remained significant, with odds ratios 6.1 (95% confidence interval 2.4 to 15.3) and 4.3 (95% confidence interval 1.7 to 10.5), respectively. Only one of the 129 individuals who suffered stroke had treated and adequately controlled hypertension. Conclusions The study illustrates the importance of adequate blood pressure control and, at the same time, that the vast majority in the population with increased blood pressure did not receive optimal care. Thus the ‘rule of halves’ still exists, and the high remaining risk in poorly treated hypertensive individuals in Sweden is remarkable and requires attention from the medical profession.

Folate, Vitamin B12, and Risk of Ischemic and Hemorrhagic Stroke A Prospective, Nested Case-Referent Study of Plasma Concentrations and Dietary Intake

Background and Purpose— Folate metabolism has been implicated in stroke. However, the possibility of a role for folate and vitamin B12, independent of their effects on homocysteine status, remains to be explored. The aim of this prospective, nested case-referent study was to relate plasma and dietary intake levels of folate and vitamin B12 to risk of stroke, taking into consideration plasma homocysteine concentrations and methylenetetrahydrofolate reductase polymorphisms. Methods— Subjects were 334 ischemic and 62 hemorrhagic stroke cases and matched double referents from the population-based Northern Sweden Health and Disease Cohort. Results— Plasma folate was statistically significantly associated with risk of hemorrhagic stroke in an inverse linear manner, both in univariate analysis and after adjustment for conventional risk factors including hypertension (odds ratio [OR] for highest versus lowest quartile 0.21 (95% confidence interval [CI], 0.06 to 0.71; P for trend=0.008)). Risk estimates were attenuated by inclusion of homocysteine in the model (OR, 0.34; 95% CI, 0.08 to 1.40; P for trend=0.088). A similar pattern was observed for increasing folate intake (multivariate OR, 0.07; 95% CI, 0.01 to 0.55; P for trend=0.031 without homocysteine, and OR, 0.16, 95% CI, 0.02 to 1.23; P for trend=0.118 with homocysteine in the analysis). We found little evidence of an association between plasma or dietary folate and risk of ischemic stroke. Neither plasma nor dietary vitamin B12 was associated with risk of either stroke subtype. Conclusions— The results of this study suggest a protective role for folate, possibly in addition to its effects on homocysteine status, in hemorrhagic but not ischemic stroke.

Chlamydia pneumoniae Antibodies and High Lipoprotein(a) Levels Do Not Predict Ischemic Cerebral Infarctions Results From a Nested Case-Control Study in Northern Sweden

BACKGROUND AND PURPOSE An association between high lipoprotein(a) [Lp(a)] levels and positive Chlamydia pneumoniae IgG titers in coronary artery disease has been described. The possibility of predicting ischemic stroke by measurements of plasma Lp(a) and C pneumoniae antibodies was investigated. METHODS This incident case-control study included 101 case subjects (cases) who had suffered ischemic cerebral infarctions and 201 matched control subjects (controls). The study population was nested within the Västerbotten Intervention Program or the WHO MONICA project. Plasma samples were measured for C pneumoniae-specific IgG and IgA antibodies and Lp(a). RESULTS A significantly higher mean Lp(a) level was found in female cases than in female controls. However, plasma Lp(a) was unable to predict ischemic cerebral infarctions in either women or men. The proportion of individuals with positive C pneumoniae-specific IgG or IgA titers did not differ between cases and controls. Antibody titers were unable to predict a future stroke. The proportion of individuals with a positive C pneumoniae IgG titer in combination with a high Lp(a) level did not differ significantly between cases and controls. CONCLUSIONS These data suggest that there is no association between baseline plasma Lp(a) levels, presence of C pneumoniae antibodies, and future ischemic cerebral infarctions. Furthermore, no evidence of an interactive effect between high Lp(a) levels and C pneumoniae IgG titers was found. However, selection bias and a recent C pneumoniae epidemic may have influenced the results.