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.
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.
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
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.
To evaluate tissue plasminogen activator (tPA) activity as a measure of fibrinolytic response to treatment with streptokinase (SK) and to relate this to the effect of pretreatment SK antibodies and to successful reperfusion assessed by continuous computerized vectorcardiography (VCG).
Umeå University Hospital.
A total of 104 patients with acute myocardial infarction (AMI) treated with SK and no history of previous SK treatment were studied. The tPA activity was measured 4 h after the start of treatment. The effect of pre-existing neutralizing antibodies to SK was analysed with a functional assay in pretreatment samples. Reperfusion was evaluated with VCG.
Fifty-five patients (53%) were classified as successfully reperfused. The risk for failed reperfusion was calculated in logistic regression models. In a univariate model, a borderline significant increase in the risk of failed reperfusion was observed in intermediate levels of SK neutralizing antibodies, but not in the highest levels. In a multivariate model, only high tPA activity, >25 U mL(-1), at 4 h (OR 0.17: 95% CI: 0.06-0.51) was associated with a higher rate of reperfusion whilst longer time to treatment (OR 1.17; 95% CI: 1.02-1.35) was associated with a higher risk of failed reperfusion. There was no significant correlation between neutralizing antibodies to SK and tPA activity at 4 h.
The SK treatment of AMI induced high levels of tPA activity which were associated with successful reperfusion. The effect of pre-existing SK antibodies had no significant influence on reperfusion and were not correlated to the fibrinolytic activity obtained.
OBJECTIVES: To determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow-up compared with baseline. DESIGN: A population-based, prospective, nested case-referent study. SETTING: Screening took place at the nearest health survey centre in northern Sweden. SUBJECTS: Of more than 36,000 persons screened, 78 developed a first myocardial infarction (average 18 months after sampling). Fifty of these had participated in a follow-up health survey (average 8(1/2) years between surveys) and were sex- and age-matched with 56 referents. MAIN OUTCOME MEASURES: Comparison of plasma homocysteine levels in case and referent subjects before and after development of a first myocardial infarction. RESULTS: No statistically significant difference was found between cases and referents regarding homocysteine at baseline or follow-up. Plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow-up but not baseline was associated with first myocardial infarction (OR 2.49; 95% CI: 1.03-6.02), but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline (OR 2.94; 95% CI: 1.05-8.21) and follow-up (OR 3.38; 95% CI: 1.21-9.48). CONCLUSION: In this study, first myocardial infarction did not cause increased plasma homocysteine concentration.
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.
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.
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.
The aim of the study was to test if plasma levels of thrombomodulin could predict mortality in 209 patients on long-term anticoagulant treatment followed up for 3.8 years.
The thrombomodulin level was 60.9 +/- 29.8 micrograms.l-1 for all 45 patients who died and 60.5 +/- 30.5 micrograms.l-1 for the 38 vascular deaths, compared to 52.3 +/- 20.7 micrograms.l-1 for the 164 survivors. We found that, in Cox regression analyses, all-cause (P = 0.025) and vascular mortality (P = 0.042) was significantly and independently associated with increased levels of thrombomodulin.
The level of plasma thrombomodulin can predict all-cause and vascular mortality in patients on long-term anticoagulant treatment.
To investigate components of the haemostatic and fibrinolytic system in borderline hypertensives and hypertensives, drug-treated or not, from a defined population.
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 or = 95 mmHg, in 8% of the subjects.
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
From the Department of Public Health and Clinical Medicine, Umeå University, Umeå Research Department, Norrbotten County Council, Luleå Department of Medicine, Skellefteå Hospital, Skellefteå Department of Medicine, Sunderby Hospital, Luleå National Board of Health and Welfare, Stockholm, Sweden.
Abstract. Eriksson M, Holmgren L, Janlert U, Jansson J-H, Lundblad D, Stegmayr B, S?derberg S, Eliasson M (Department of Public Health and Clinical Medicine, Ume? University, Ume?; Research Department, Norrbotten County Council, Lule?; Department of Medicine, Skellefte? Hospital, Skellefte?; Department of Medicine, Sunderby Hospital, Lule?; and National Board of Health and Welfare, Stockholm, Sweden). Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986-2009. J Intern Med 2011; 269: 219-231. 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 10 586 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.