| 1. |
- Lundblad, Dan, et al.
(författare)
-
Low level of tissue plasminogen activator activity innon-diabetic patients with a first myocardial infarction
- 2005
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 258:1, s. 13-20
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors. Design. Case-control study in northern Sweden. Subjects. A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty-seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow-up, giving a final number of 88 patients, 73 men and 15 women. Patients were age- and sex matched with control subjects drawn from the local cohort in the MONICA population survey 1994. Main outcome measures. We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR). Results. PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR = 19.1; CI 3.0-123) together with the highest quartiles of fibrinogen (OR = 25; CI 5.2-120) but other variables were not. Conclusion. Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables
|
|
| 2. |
- Rautio, Aslak, 1962-
(författare)
-
Diabetes Mellitus and Cardiovascular Risk : epidemiology, etiology and intervention
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Framingham Study from 1988 showed a heavy impact of diabetes mellitus (DM) on the risk and prognosis of cardiovascular disease (CVD). Several other studies have confirmed that DM is an independent risk factor for coronary heart disease (CHD) and that patients with DM have a poor prognosis. However, the strength of DM as a risk factor is debated. Some studies indicate that DM, as a risk factor for a coronary event, is comparable to already known or established CHD. Also, mechanisms of how diabetes increases the CVD risk are under intensive research. A novel risk factor such as altered fibrinolysis is one of the potential mechanisms explaining the heavy cardiovascular burden in diabetes. Hypofibrinolytic changes can be seen in individuals with metabolic syndrome, insulin resistance, and obesity as well as in patients with manifest diabetes or manifest CHD.Methods: This dissertation is divided in three parts; epidemiological, etiological and interventional. Papers I and II are epidemiological, population based retrospective studies which compare time trends in myocardial infarction and stroke morbidity and mortality between patients with or without diabetes. Papers III and IV have an etiological approach to the fibrinolytic system and CVD risk both in patients with or without diabetes. Paper V is the interventional part of this thesis studying if intensive insulin treatment can improve fibrinolysis in patients with high CVD risk.Results: The incidence and mortality from myocardial infarction and stroke have declined in the counties of Västerbotten and Norrbotten in Northern Sweden. Unfortunately, the subgroup with patients with diabetes and myocardial infarction (MI) in Paper I did not benefit from these favorable trends over the study period. For stroke, this is for the first time declining incidence has been reported in this population. Incidence of first-ever stroke decreased for non-diabetic men with a yearly change of -0.8 percent (p-value <0.001), and for diabetic women with a yearly change of -1.5 percent (p-value=0.012). Recurrent stroke incidence declined highly significant, p-value <0.001, for non-diabetic men and women and for diabetic women with a yearly change of -1.5, -2.7, and -5.4 percent, respectively. For diabetic men a non-significant decline of -1.0 percent (p-value=0.28) in stroke incidence was seen. Paper II showed that women with diabetes had decreased incidence for stroke but not men with diabetes. Also, reduced mortality from stroke was found in all patients except for diabetic women with first ever stroke.Patients with diabetes have altered fibrinolysis compared to individuals with normal glucose metabolism. Also, patients with prior MI manifest a hypofibrinolytic stage with low tissue-type plasminogen activator (tPA) activity and high levels of plasminogen activator inhibitor-1 (PAI-1) and fibrinogen. Paper III showed a significant association between decreased tPA activity and increased fibrinogen levels in patients with a first MI when examined 3 months after the event. The results persisted even after adjustment for traditional risk factors and variables mirroring the insulin resistance syndrome and were significant in the whole study group of subjects with MI as well as for men alone.Paper IV, a 10 year follow-up study, showed that in patients with diabetes, tPA-activity significantly predicted the presence of sign(s) of lower extremity arterial disease (LEAD) at the baseline and at the 10-year follow-up. In addition, tPA-mass at the 10-year follow-up was associated with signs of LEAD. Baseline age, hypertension, and HbA1c were independently associated with sign(s) of LEAD at 10 years. This long-term study supports previous findings of a significant association between asymptomatic LEAD and tPA-activity. Thus, tPA-activity may be an early marker of LEAD, although the mechanism of this relationship remains unclear.Several studies report conflicting results regarding benefits and disadvantages of intensive insulin treatment. ORIGIN trial was an international multicenter trial studying effects of intensive insulin treatment on CVD. This thesis reports a Swedish sub-study of ORIGIN trial examining effects of insulin treatment on fibrinolysis. The allocation to insulin treatment did not significantly affect the studied fibrinolytic markers or von Willebrand factor (VWF) compared to the standard treatment. Log mean delta values between baseline and end of study increased significantly for tissue plasminogen activator activity (tPAact) and tPA/PAI-1 complex. For plasminogen activator inhibitor-1 (PAI-1), tPA antigen (tPAag) and VWF no significant differences were found. Within-group analysis during the whole study period revealed significant changes for tPA/PAI-1 complex, tPA antigen, and VWF in the insulin treatment group but no significant changes in the standard treatment group.The hypothesis that allocation to insulin treatment would improve the levels of markers of fibrinolysis or VWF compared to standard glucose lowering treatment could not be verified. Conclusion: This dissertation shows that patients with diabetes still have a heavy cardiovascular disease burden with increased risk for MI and stroke compared to individuals with normal glucose metabolism. This cardiovascular burden also includes increased morbidity, mortality, and poorer long-term prognosis. The fibrinolytic system has an impact on cardiovascular disease and this thesis has shown that patients with diabetes have unfavorable changes in their fibrinolysis and that alterations in fibrinolysis can predict future peripheral artery disease. However, intensive insulin therapy did not appear to affect this system to the extent of resulting in reduced cardiovascular morbidity.
|
|
| 3. |
- Rautio, Aslak, et al.
(författare)
-
Favorable Trends in the Incidence and Outcome in Stroke in Nondiabetic and Diabetic Subjects Findings From the Northern Sweden MONICA Stroke Registry in 1985 to 2003
- 2008
-
Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 39:12, s. 3137-3144
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Several studies indicate a declining case-fatality and mortality in stroke. Little is known about time trends in stroke for subjects with diabetes. The purpose of this study was to compare time trends in incidence, case-fatality and mortality for stroke patients with or without diabetes. METHODS: This study was based on the Northern Sweden MONICA Project Stroke registry during 1985 to 2003. 15 382 patients, aged 35 to 74 years, were included in the study. 11 605 had a first-ever stroke and 3777 had a recurrent stroke. In both men and women previously diagnosed diabetes was found in 22.8%. RESULTS: The incidence of stroke was 5 and 8 times higher in diabetic subjects than in nondiabetics, in men and women, respectively. Incidence of first-ever stroke decreased for nondiabetic men, probability value <0.001, and for diabetic women, probability value=0.012. Recurrent stroke incidence declined highly significant, probability value <0.001, in all but diabetic men. For diabetic women, the decrease in incidence in first and recurrent stroke was significantly greater than in nondiabetic women. Case-fatality and mortality in stroke declined for all groups except diabetic women with first-ever stroke. The time trends in case fatality and mortality did not differ significantly between nondiabetic and diabetic patients. CONCLUSIONS: The incidence of stroke declined in both nondiabetic and diabetic subjects except for diabetic men and for nondiabetic women with first-ever stroke. Case-fatality in first-ever stroke declined for all but diabetic women. This led to a decreased mortality over the 19-year period for both groups. This is the first time that the decline in stroke incidence is reported in this MONICA population.
|
|
| 4. |
- Rautio, Aslak, et al.
(författare)
-
Favourable trends in the incidence and outcome ofmyocardial infarction in nondiabetic, but not in diabetic, subjects : findings from the MONICA myocardial infarctionregistry in northern Sweden in 1989–2000
- 2005
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 258:4, s. 369-377
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to comparetime trends in incidence, case fatality and mortalitydue to myocardial infarction (MI) in patients with orwithout diabetes.Methods: This study was based on the Northe rnSweden MONICA Project MI registry with a targetpopulation of about 200 000 inhabitants in the agegroup 35–64 years in the two northernmostcounties of Sweden. During 1989–2000, 6254patients who had had an MI according to MONICAcriteria were included in this study: 4569 patientshad a first MI and 1685 had a recurrent MI. Sixteenper cent of the men and 20% of the women had haddiabetes mellitus diagnosed prior the MI.Results: Over the 12-year period, there was adeclining trend in incidence and case fatality infirst MI. Also, the event rates (first ever andrecurrent MI) decline d in men without diabetes. Inwomen without diabetes favourable time trendswere seen in first ever MI, recurrent MI and in casefatality. There were no favourable time trends forany of these outcomes in patients with diabetes.Conclusion: In nondiabetic subjects belo w the age of65, the inc idence of, and case-fatality in, MIdeclined. This led to a decreased mortality over the12-year period. These favourable trends over timewere not observed in diabetic subjects.Keywords: acute myocardial infarction, diabetesmellitus, incidence, mortali ty, time trends
|
|
| 5. |
- Rautio, Aslak, 1962-, et al.
(författare)
-
Markers of fibrinolysis may predict development of lower extremity arterial disease in patients with diabetes : A longitudinal prospective cohort study with 10 years of follow-up
- 2016
-
Ingår i: Diabetes & Vascular Disease Research. - : SAGE Publications. - 1479-1641 .- 1752-8984. ; 13:3, s. 183-191
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A previous cross-sectional study suggested that tissue plasminogen activator-activity might be an early marker of asymptomatic lower extremity arterial disease, but the long-term relationship is unknown.SUBJECTS AND METHODS: This study included 96 diabetic (48 type 1/48 type 2) and 62 non-diabetic subjects aged 30-70 years without previously known lower extremity arterial disease (age: 50.3 ± 9.3 years, gender: M/W 47.5/52.5% and body mass index: 26.6 ± 4.5 kg/m(2)). The relationships between asymptomatic lower extremity arterial disease and fibrinolytic markers (tissue plasminogen activator-activity, tissue plasminogen activator-mass, plasminogen activator inhibitor-1 activity) at baseline and after 10 years were assessed by logistic regression analysis adjusting for age, hypertension, statin treatment, HbA1c, triglycerides and low-density lipoprotein cholesterol as fixed covariates.RESULTS: The tissue plasminogen activator-activity at baseline and at the 10-year follow-up significantly predicted the presence of sign(s) of lower extremity arterial disease (odds ratio = 1.78, 95% confidence interval: 1.02-3.10, p = 0.043 and odds ratio = 1.78, 95% confidence interval: 1.12-2.23, p = 0.014, respectively). In addition, tissue plasminogen activator-mass at the 10-year follow-up was associated with signs of lower extremity arterial disease (odds ratio = 1.07, 95% confidence interval: 1.00-1.15, p = 0.046). Baseline age, hypertension and HbA1c were independently associated with sign(s) of lower extremity arterial disease at 10 years (odds ratio = 1.09, 95% confidence interval: 1.04-1.14, p = < 0.001; odds ratio = 3.68, 95% confidence interval: 1.67-8.12, p = 0.001 and odds ratio = 1.54, 95% confidence interval: 1.21-1.95, p = < 0.001, respectively).CONCLUSION: This long-term study supports previous findings of a significant association between asymptomatic lower extremity arterial disease and tissue plasminogen activator-activity. Thus, tissue plasminogen activator-activity may be an early marker of lower extremity arterial disease although the mechanism of this relationship remains unclear.
|
|
| 6. |
- Rautio, Aslak, et al.
(författare)
-
The effect of basal insulin glargine on the fibrinolytic system and von Willebrand factor in people with dysglycaemia and high risk for cardiovascular events : Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial
- 2017
-
Ingår i: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 14:4, s. 345-352
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.
|
|
