Seroprevalence of Sindbis virus and associated risk factors in northern Sweden.

Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever and arthritis which often leads to long-lasting arthralgia. To determine the seroprevalence of SINV and associated risk factors in northern Sweden, a randomly selected population aged between 25 and 74 years were invited to join the MONICA study. Serum from 1611 samples were analysed for specific IgG antibodies. Overall, 2·9% had IgG against SINV. More men (3·7%) than women (2·0%) were SINV seropositive (P = 0·047) and it was more common in subjects with a lower educational level (P = 0·013) and living in small, rural communities (P < 0·001). Seropositivity was associated with higher waist circumference (P = 0·1), elevated diastolic blood pressure (P = 0·037), and history of a previous stroke (P = 0·011). In a multiple logistic regression analysis, adjusting for known risk factors for stroke, seropositivity for SINV was an independent predictor of having had a stroke (odds ratio 4·3, 95% confidence interval 1·4-13·0, P = 0·011).

A rightward shift of the distribution of fasting and post-load glucose in northern Sweden between 1990 and 2009 and its predictors. Data from the Northern Sweden MONICA study.

AIMS: Most Swedish studies show stable diabetes prevalence despite increasing obesity, but glucose levels may shift upwards below the diagnostic threshold for diabetes. Our aim was to explore trends in glucose distribution in northern Sweden; whether these trends were uniformly distributed throughout the spectrum of glucose concentrations; and to relate trends to traditional risk factors and the obesity-related adipokine leptin. METHODS: The project consisted of four cross-sectional surveys between 1990 and 2009, with 7069 participants aged 25-64 years. The overall participation rate was 74.4%. Trend analyses of glucose concentrations along the entire distribution and linear regression in relation to survey years and risk markers were used. RESULTS: Fasting and post-load glucose increased in women (both P < 0.001) and post-load glucose in men (P = 0.004). The increase was seen in most deciles of glucose concentrations. The prevalence of impaired glucose tolerance doubled in women to 14.5% and tripled in men to 10.1% (both P = 0.004). The prevalence of impaired fasting glucose rose in women from 4.5 to 7.7% (P < 0.001). The prevalence of diabetes was unchanged-6.4% in 2009. In men, leptin, together with traditional risk factors, explained 7.8 and 10.8% of the variance in fasting (P = 0.008) and post-load (P < 0.001) glucose, respectively. CONCLUSIONS: Increasing fasting and post-load glucose concentrations were seen in most deciles of the glucose distribution, indicating a shift in the entire population. Leptin was significantly associated with fasting and post-load glucose in men.

Patients with diabetes are not more likely to have atypical symptoms when seeking care of a first myocardial infarction. An analysis of 4028 patients in the Northern Sweden MONICA Study.

AIM: To describe symptoms of a first myocardial infarction in men and women with and without diabetes. METHODS: We conducted a population-based study of 4028 people aged 25-74 years, with first myocardial infarction registered in the Northern Sweden Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) myocardial infarction registry between 2000 and 2006. Symptoms were classified as typical or atypical according to the World Health Organization MONICA manual. RESULTS: Among patients with diabetes, 90.1% reported typical symptoms of myocardial infarction; the corresponding proportion among patients without diabetes was 91.5%. In the diabetes group, 88.8% of women and 90.8% of men had typical symptoms of myocardial infarction. No differences were found in symptoms of myocardial infarction between women with and without diabetes or between men with and without diabetes. Atypical symptoms were more prevalent in the older age groups (> 65 years) than in the younger age groups (< 65 years). The increases were approximately equal among men and women, with and without diabetes. Diabetes was not an independent predictor for having atypical symptoms of myocardial infarction. CONCLUSIONS: Typical symptoms of myocardial infarction were equally prevalent in patients with and without diabetes and there were no sex differences in symptoms among persons with diabetes. Diabetes was not a predictor of atypical symptoms.

The disparity between long-term survival in patients with and without diabetes following a first myocardial infarction did not change between 1989 and 2006: an analysis of 6,776 patients in the Northern Sweden MONICA Study.

AIMS/HYPOTHESIS: Long-term survival after myocardial infarction (MI) has improved in the population, but data on diabetic patients is lacking. We analysed survival for up to 18 years after a first MI in patients with or without diabetes. METHODS: The Northern Sweden MONICA Myocardial Infarction Registry was linked to the Cause-of-Death Registry for a total of 6,776 patients, 25-64 years of age, with a first MI during 1989-2006. Prehospital deaths were included. Follow-up ended on 30 August 2008. RESULTS: Sixteen per cent had diabetes. Median follow-up time was 6.8 years, and the study included 50,667 patient-years. One third of the non-diabetic patients died vs half of the diabetic patients. Median survival for non-diabetic men was 227 months and for diabetic men 123 months. Corresponding figures for the non-diabetic and diabetic women were 222 and 81 months respectively. Men with diabetes had an age-adjusted HR for all-cause mortality of 1.56 (95% CI 1.39, 1.79) vs men without diabetes. Mortality risk was higher among diabetic women, HR 1.97 (1.62, 2.39) (diabetes × sex interaction, p = 0.03). Survival increased for three consecutive cohorts and was higher in non-diabetic patients for all durations of follow-up and in all three cohorts. The interaction of diabetes x cohort was not significant over time (p = 0.5) and HRs did not differ either. CONCLUSIONS/INTERPRETATION: Long-term survival after a first MI is markedly lower in diabetic patients, especially among women, over an 18-year observation time. Although survival has improved in diabetic patients, the effect of diabetes upon mortality has not diminished.

The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes.

AIMS/HYPOTHESIS: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors. METHODS: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques. RESULTS: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726-0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity. CONCLUSIONS/INTERPRETATION: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.

Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986-2009.

OBJECTIVES: the incidence of cardiovascular disease has declined rapidly in Sweden since the 1980s. We explored changes in major cardiovascular risk factors in northern Sweden between 1986 and 2009. DESIGN: since 1986, six population surveys have been carried out in northern Sweden using procedures of the World Health Organization MONICA project. The population age range was 25-64 years in 1986 and 1990, and 25-74 years from 1994. Trends were analysed using generalized linear models. RESULTS: a total of 10586 subjects were included in the surveys. Blood pressure decreased by 4.9/3.9 mmHg in women and 1.8/1.5 mmHg in men aged 25-64 years between 1986 and 2009. In men and women aged 65-74 years, the decrease was 12.6/6.1 mmHg between 1994 and 2009. From 1994, the use of blood pressure-lowering drugs increased, particularly among the older subgroup. The prevalence of smoking halved between 1986 and 2009; 11% of women and 9% of men were smokers in 2009. Cholesterol levels decreased by 0.9 mmol L(-1) in the younger age group (25-64 years), and the use of lipid-lowering agents increased from 1994. Among subjects aged 25-64 years, one in five was obese in 2009, which was twice as many as in 1986, and body mass index (BMI) increased by 1.5 kg m(-2) , corresponding to an increase in weight of 4 kg. There was no further increase in BMI from 2004. The prevalence of diabetes did not change between 1986 and 2009. The proportion that received a university education increased markedly in all age groups, especially in women, during the study period. CONCLUSIONS: significant improvements were observed in major cardiovascular risk factors in northern Sweden between 1986 and 2009.

Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia.

Nitric oxide (NO) and peroxynitrite, formed from NO and superoxide anion, have been implicated as mediators of neuronal damage following focal ischemia, but their molecular targets have not been defined. One candidate pathway is DNA damage leading to activation of the nuclear enzyme, poly(ADP-ribose) polymerase (PARP), which catalyzes attachment of ADP ribose units from NAD to nuclear proteins following DNA damage. Excessive activation of PARP can deplete NAD and ATP, which is consumed in regeneration of NAD, leading to cell death by energy depletion. We show that genetic disruption of PARP provides profound protection against glutamate-NO-mediated ischemic insults in vitro and major decreases in infarct volume after reversible middle cerebral artery occlusion. These results provide compelling evidence for a primary involvement of PARP activation in neuronal damage following focal ischemia and suggest that therapies designed towards inhibiting PARP may provide benefit in the treatment of cerebrovascular disease.

Abdominal and gynoid adipose distribution and incident myocardial infarction in women and men.

OBJECTIVE: The relationships between objectively measured abdominal and gynoid adipose mass with the prospective risk of myocardial infarction (MI) has been scarcely investigated. We aimed to investigate the associations between fat distribution and the risk of MI. SUBJECTS: Total and regional fat mass was measured using dual-energy X-ray absorptiometry (DEXA) in 2336 women and 922 men, of whom 104 subsequently experienced an MI during a mean follow-up time of 7.8 years. RESULTS: In women, the strongest independent predictor of MI was the ratio of abdominal to gynoid adipose mass (hazard ratio (HR)=2.44, 95% confidence interval (CI) 1.79-3.32 per s.d. increase in adipose mass), after adjustment for age and smoking. This ratio also showed a strong association with hypertension, impaired glucose tolerance and hypertriglyceridemia (P<0.01 for all). In contrast, the ratio of gynoid to total adipose mass was associated with a reduced risk of MI (HR= 0.57, 95% CI 0.43-0.77), and reduced risk of hypertension, impaired glucose tolerance and hypertriglyceridemia (P<0.001 for all). In men, gynoid fat mass was associated with a decreased risk of MI (HR=0.69, 95% CI 0.48-0.98), and abdominal fat mass was associated with hypertriglyceridemia (P for trend 0.02). CONCLUSION: In summary, fat distribution was a strong predictor of the risk of MI in women, but not in men. These different results may be explained by the associations found between fat distribution and hypertension, impaired glucose tolerance and hypertriglyceridemia.

Consumption of filtered and boiled coffee and the risk of first acute myocardial infarction; a nested case/referent study.

BACKGROUND AND AIM: In northern Sweden, consumption of both filtered and boiled coffee is common. Boiled coffee, especially popular in rural areas, is known to raise blood lipids, a risk factor for acute myocardial infarction (MI). To our knowledge, only one epidemiological study, a case-control study from Sweden, has investigated boiled coffee in MI, noting an increased risk at high consumption levels in men, and no association in women. The aim of the present nested case-referent study was to relate consumption of filtered and boiled coffee to the risk of first MI. METHODS AND RESULTS: The study subjects were 375 cases (303 men, 72 women) and 1293 matched referents from the population-based Northern Sweden Health and Disease Study. Coffee consumption was assessed by food frequency questionnaire. Risk estimates were calculated by conditional logistic regression. A statistically significant positive association was found between consumption of filtered coffee and MI risk in men [odds ratio for consumption > or = 4 times/day versus < or = 1 time/day 1.73 (95% CI 1.05-2.84)]. In women, a similar association was observed, but for boiled coffee [odds ratio 2.51 (95% CI 1.08-5.86)]. After adjustment for current smoking, postsecondary education, hypertension, and sedentary lifestyle, the results for women were no longer statistically significant. CONCLUSION: Consumption of filtered coffee was positively associated with the risk of a first MI in men. A similar tendency was observed for boiled coffee in women, but the result was not statistically significant in multivariate analysis. Further investigation in a larger study is warranted.

Plasma folate and total homocysteine levels are associated with the risk of myocardial infarction, independently of each other and of renal function.

OBJECTIVES: To investigate the relationship between plasma folate, vitamin B12 and total homocysteine concentrations, dietary intake of folate and vitamins B12, B6 and B2, and the risk of first acute myocardial infarction (MI). DESIGN: Nested case-referent study with up to 13 years of follow-up. SETTING: The population-based Northern Sweden Health and Disease Study, with 73 879 participants at the time of case ascertainment. SUBJECTS: A total of 571 MI cases (406 men) and 1569 matched referents. Of the cases, 530 had plasma samples available, and 247 had dietary B-vitamin intake data. RESULTS: Plasma concentrations of folate were inversely associated, and total homocysteine positively associated, with the risk of MI, independently of each other and of a number of established and novel cardiovascular risk factors, including renal function [multivariate odds ratio for highest vs. lowest quintile of folate 0.52 (95% CI 0.31-0.84), P for trend = 0.036, and homocysteine 1.92 (95% CI 1.20-3.09), P for trend = 0.006]. For plasma vitamin B12 concentrations, and vitamin B12, B6 and B2 intake, no clear risk relationship was apparent. Though not statistically significant, the results for folate intake were consistent with those for plasma concentrations. CONCLUSIONS: In this large prospective study of a population without mandatory folic acid fortification, both folate and homocysteine were strongly associated with the risk of myocardial infarction, independently of each other and of renal function. Although randomized trials of folic acid supplementation are needed to determine causality, our findings highlight the potential importance of folate, or sources of folate, in incident cardiovascular disease.

Reticular stimulation and chlorpromazine: an animal model for schizophrenic overarousal.

It has been postulated that certain schizophrenic patients are in a state of continual central excitation and that improvement in these patients after treatment with chlorpromazine is a result of the action of the drug in reducing this excitation. A model was developed to test this postulated state of central excitation. Rats were electrically stimulated in the mesencephalic reticular formation while performing a simple attention task. Stimulation or treatment with chlorpromazine impaired the performance of the animals; however, the two treatments together resulted in performance indistinguishable from that seen after injections of saline alone.

CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95.

Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotransmitter release, neurotoxicity, and cyclic GMP elevations. The coupling of NMDA receptor-mediated calcium influx and nNOS activation is postulated to be due to a physical coupling of the receptor and the enzyme by an intermediary adaptor protein, PSD95, through a unique PDZ-PDZ domain interaction between PSD95 and nNOS. Here, we report the identification of a novel nNOS-associated protein, CAPON, which is highly enriched in brain and has numerous colocalizations with nNOS. CAPON interacts with the nNOS PDZ domain through its C terminus. CAPON competes with PSD95 for interaction with nNOS, and overexpression of CAPON results in a loss of PSD95/nNOS complexes in transfected cells. CAPON may influence nNOS by regulating its ability to associate with PSD95/NMDA receptor complexes.

Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neural damage.

Nitric oxide (NO) is a new intercellular messenger that occurs naturally in the brain without causing overt toxicity. Yet, NO has been implicated as a mediator of cell death in cell death. One explanation is that ischemia causes overproduction of NO, allowing it to react with superoxide to form the potent oxidant peroxynitrite. To address this question, we used immunohistochemistry for citrulline, a marker for NO synthase activity, and 3-nitrotyrosine, a marker for peroxynitrite formation, in mice subjected to reversible middle cerebral artery occlusion. We show that ischemia triggers a marked augmentation in citrulline immunoreactivity but more so in the peri-infarct than the infarcted tissue. This increase is attributable to the activation of a large population (approximately 80%) of the neuronal isoform of NO synthase (nNOS) that is catalytically inactive during basal conditions, indicating a tight regulation of physiological NO production in the brain. In contrast, 3-nitrotyrosine immunoreactivity is restricted to the infarcted tissue and is not present in the peri-infarct tissue. In nNOS(Delta/Delta) mice, known to be protected against ischemia, no 3-nitrotyrosine immunoreactivity is detected. Our findings provide a cellular localization for nNOS activation in association with ischemic stroke and establish that NO is not likely a direct neurotoxin, whereas its conversion to peroxynitrite is associated with cell death.

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.

Structural and functional analysis of the human IgG-Fab receptor activity of streptococcal protein G.

Streptococcal protein G (SPG) shows specific binding activity to IgGs and serum albumins from various species. In order to investigate the structural domains of SPG responsible for the specific interaction with human IgG-Fab, the binding characteristics of a collection of recombinant receptors were analysed. The study includes receptors comprising different parts of the SPG molecule as well as chimeric receptors containing IgG-binding domains of staphylococcal protein A (SPA) fused to the N-terminal AB-region of SPG, which has been claimed to interact with human IgG-Fab. Purified defined gene products were allowed to compete for the binding to human IgG, human IgG-F(ab')2 fragments and human serum albumin (HSA) in several sets of competitive binding experiments. The results demonstrate that the C-terminal C domains have both IgG-Fc- and IgG-Fab-binding capacities, whereas the N-terminal AB region is responsible for the HSA-binding only. These results, which are in conflict with previous work, demonstrate that the binding to both the IgG-Fc and the IgG-Fab region is mediated by the same structurally distinct receptor region of SPG.

Proinsulin, intact insulin, and fibrinolytic variables and fibrinogen in healthy subjects. A population study.

OBJECTIVE: As high serum insulin predicts impaired fibrinolysis and proinsulin reacts in most conventional insulin assays, we hypothesized that proinsulin could link low fibrinolytic activity and hyperinsulinemic conditions. RESEARCH DESIGN AND METHODS: We explored the relationship between fibrinolysis and plasma fibrinogen on the one hand and specific insulin and proinsulin on the other, in a healthy population sample of 165 men and women, 25-74 years of age, from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Study. Specific insulin and proinsulin were measured by enzyme-linked immunosorbent assay. Partial correlation coefficients, adjusted for age and sex, were calculated. RESULTS: Plasma fibrinogen levels were related to insulin (r = 0.25, P < 0.01) and proinsulin (r = 0.29, P < 0.001), as was plasminogen activator inhibitor (PAI)-1 activity (r = 0.36 and r = 0.29, respectively; P < 0.001). Tissue Plasminogen activator (tPA) activity correlated inversely to insulin (r = 0.35, P < 0.001) and proinsulin (r = - 0.36, P < 0.001). In a multivariate analysis taking also smoking and anthropometric and metabolic measurements into account, fasting proinsulin was a significant predictor of high plasma fibrinogen level. Insulin and proinsulin levels were not related to tPA activity. High levels of postload insulin, triglycerides, and diastolic blood pressure, but not proinsulin, predicted high PAI-l activity. CONCLUSIONS: In a healthy population, the relationship previously described between high insulin levels and impaired fibrinolysis is not attributable to confounding from proinsulin. Elevated proinsulin levels are associated with high fibrinogen levels.

High proinsulin levels precede first-ever stroke in a nondiabetic population.

BACKGROUND AND PURPOSE: Diabetic subjects have a 3- to 6-fold increased risk for stroke compared with nondiabetic subjects, and hyperinsulinemia shows strong and consistent associations with a cluster of cardiovascular risk factors. Methods separating proinsulin from (true) insulin have demonstrated proinsulin to be more strongly associated with cardiovascular disease than insulin. The present study evaluates the associations between first-ever stroke, proinsulin, and insulin. METHODS: In this incident case-referent study of a nondiabetic population, 94 cases of first-ever stroke (59 men and 35 women) were individually age- and sex-matched to 178 referents. Blood sampling was collected before the stroke event. Proinsulin and insulin were measured with highly sensitive 2-site sandwich enzyme-linked immunosorbent assays. RESULTS: In the study population, high proinsulin concentration more than tripled the risk for first-ever stroke after adjustments for total cholesterol, systolic blood pressure, smoking, body mass index, and insulin, with an odds ratio of 3.4 (95% CI, 1.4 to 8.4). In women the risk was even more pronounced, with an odds ratio of 13.7 (95% CI, 1.3 to 146). Synergy was found between proinsulin and systolic blood pressure. In women, synergy was also found between proinsulin and diastolic blood pressure as well as between insulin and both blood pressures. CONCLUSIONS: High levels of proinsulin may predict later occurrence of first-ever stroke in a nondiabetic population.

Relationship of cigarette smoking and snuff dipping to plasma fibrinogen, fibrinolytic variables and serum insulin. The Northern Sweden MONICA Study.

The influence of cigarette smoking and use of smokeless tobacco on plasma fibrinogen level, fibrinolytic variables, glucose tolerance and serum insulin was studied in a randomly selected population sample consisting of 604 men and 662 females between 25 and 64 years. Subjects were grouped according to tobacco habits as follows: regular smokers (> 1 cig/day), ex-smokers, snuff dippers, and non-tobacco users. An oral glucose tolerance test was performed on 54% of the participants. Tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) activity were used to study fibrinolysis. Men who smoked had 0.34 g/l (95% CI 0.17 to 0.49) higher fibrinogen level than non-tobacco users and numbers of cigarettes smoked correlated with plasma fibrinogen levels (r = 0.21, P = 0.006). Female smokers had significantly higher fibrinogen levels than ex-smokers but the difference compared with non-smokers was not significant. Snuff dipping did not affect fibrinogen levels. We found no relationship between tPA activity, PAI-1 activity and tobacco use. Post-load plasma glucose was lower in women who smoked, otherwise no influence of tobacco use on glucose levels was seen. Lower post-load insulin levels (-8.8 mU/ml, 95% CI -2.4 to -16.3) than in non-smokers were also found in women who smoked. This was only partially explained by a lower body mass index in smokers. We conclude that cigarette smoking is associated with increased fibrinogen levels, unaltered fibrinolysis, normal glucose tolerance and insulin levels. The use of smokeless tobacco, as moist oral snuff, does not appear to affect these potential cardiovascular risk factors.

Increased levels of tissue plasminogen activator antigen in essential hypertension. A population-based study in Sweden.

OBJECTIVE: To investigate components of the haemostatic and fibrinolytic system in borderline hypertensives and hypertensives, drug-treated or not, from a defined population. DESIGN AND METHODS: A randomly selected sample of the population of northern Sweden, 1558 subjects aged 25-64 years, was studied. Eight per cent of them were being treated with antihypertensive drugs (trHT). Remaining subjects were classified according to their mean diastolic blood pressure (DBP). Normotension, DBP < 85 mmHg, was found in 63%, borderline hypertension (bHT), DBP 85-94 mmHg, in 21% and untreated hypertension (uHT), DBP > or = 95 mmHg, in 8% of the subjects. RESULTS: Mean age increased from the normotensive group through the bHT and uHT groups to the trHT group, members of which were the oldest. Age-adjusted values for the body mass index, waist: hip ratio, serum triglyceride and Phadeseph plasma insulin levels increased with each level of hypertension. Plasma fibrinogen levels and plasminogen activator inhibitor type 1 activity (in men) increased stepwise from normotensives through bHT and uHT to the highest values found in the trHT group. The tissue plasminogen activator (tPA) activity in men declined strongly across the groups, trHT having the lowest fibrinolytic activity (P < 0.001). tPA antigen levels increased strongly from normotensives through bHT to uHT, but then were lower in the trHT group. Even after adjustment for possible confounders, men in the uHT group had 21% higher (P = 0.027) tPA antigen levels than did the normotensives. In bHT men, the tPA antigen and plasminogen activator inhibitor type 1 activities were 14 and 24% respectively, higher (P < 0.01) than those in the normotensives. CONCLUSION: Hypertension is associated with multiple metabolic and fibrinolytic disturbances that are accentuated in drug-treated hypertensives and already discernible in subjects with borderline hypertension. Decreased fibrinolysis is associated with, and possibly secondary to, metabolic disturbances linked to the insulin-resistance syndrome. The independent increase in tPA antigen in hypertensive men might indicate an endothelial dysfunction.