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Risk markers for a first myocardial infarction
Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of a first myocardial infarction is associated with a large number of contributing factors. Age, male sex, hypertension, smoking, diabetes, body mass index and hypercholesterolemia are considered as established risk factors.

The primary aim of the present dissertation was to evaluate whether specific biomarkers could improve the prediction of subjects at risk for a first myocardial infarction when considered in addition to established cardiovascular risk factors. The biomarkers investigated include: tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), von Willebrand factor (VWF), dehydroepiandrosterone sulfate (DHEAS), lipoprotein (a) (Lp(a)), leptin, apolipoproptein A1 (ApoA1), proinsulin, homocysteine and homozygosity for the 5,10- methylenetetrahydrofolate reductase (MTHFR) C>T genotype. A secondary objective was 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 to baseline.

The study population consisted of 36 405 subjects screened and included in the Västerbotten Intervention Program and the Northern Sweden MONICA cohorts between January 1, 1985 and September 30, 1994. A nested incident case-referent study design was used. Seventy eight cases with a first myocardial infarction were identified, and from the same cohort twice as many sex and age matched referents were randomly selected. Moreover, a follow-up health survey (average 8.5 years between surveys) was conducted with 50 cases and 56 matched referents.

High plasma levels of tPA and PAI-1 mass concentration, VWF, proinsulin, leptin and Lp(a) and low plasma levels of ApoA1 were associated with subsequent development of a first myocardial infarction in univariate conditional logistic regression analysis. 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 was independent of established risk factors. In women, high plasma concentrations of TM were associated with significant increases in risk of a first myocardial infarction. No predictive values of DHEAS, homocysteine or for the point mutation C677>T in the gene for MTHFR was found regarding the risk of a first myocardial infarction. The summarised importance of haemostatic and metabolic variables (proinsulin, lipids including Lp(a) and leptin) in predicting first myocardial infarction in men, as well as possible interactions among these variables, were studied. High tPA and Lp(a) and low ApoA1 remained significant risk markers in multivariate analysis independent of established risk factors. There were non-significant synergic interactions between high Lp(a) and leptin and tPA respectively, and between high Lp(a) and low ApoA1.

In the follow-up study 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 at baseline was associated with first myocardial infarction 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 and follow-up.

In conclusion, the present results support the hypothesis that biomarkers, in addition to the traditional cardiovascular risk factors, carry predictive information on the risk of developing a first myocardial infarction.

Place, publisher, year, edition, pages
Umeå: Folkhälsa och klinisk medicin , 2005. , 107 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 975
Keyword [en]
haemostatis, lipoprotein (a), MTHFR, homocysteine, proinsulin, leptin, apolipoprotein A1, DHEAS, myocardial infarction, risk factors
Identifiers
URN: urn:nbn:se:umu:diva-603ISBN: 91-7305-909-9 (print)OAI: oai:DiVA.org:umu-603DiVA: diva2:143943
Public defence
2005-09-16, sal D, Tandläkarhögskolan, 9tr., Umeå, 09:00 (English)
Opponent
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2009-11-30Bibliographically approved
List of papers
1. 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
Open this publication in new window or tab >>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
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1998 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 98, no 21, 2241-2247 p.Article in journal (Refereed) Published
Abstract [en]

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.

Identifiers
urn:nbn:se:umu:diva-4719 (URN)9826309 (PubMedID)
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2017-12-14Bibliographically approved
2. 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
Open this publication in new window or tab >>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
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2001 (English)In: Coronary Artery Disease, ISSN 0954-6928, E-ISSN 1473-5830, Vol. 12, no 2, 85-90 p.Article in journal (Refereed) Published
Abstract [en]

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.

Identifiers
urn:nbn:se:umu:diva-4720 (URN)11281306 (PubMedID)
Available from: 2005-09-29 Created: 2005-09-29 Last updated: 2017-12-14Bibliographically approved
3. Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction.
Open this publication in new window or tab >>Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction.
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2004 (English)In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 11, no 1, 33-40 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The summarized importance of haemostatic and metabolic variables (insulin, lipids including lipoprotein (a) [Lp(a)] and leptin) in predicting first myocardial infarction, as well as possible interactions among these variables, have not been reported. DESIGN: A prospective case-control study nested within the Northern Sweden Health and Disease Cohort. METHODS: Sixty-two men diagnosed with a first myocardial infarction were sex- and age-matched with 124 controls. Conditional logistic regression was conducted including established risk factors, plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) mass concentration, von Willebrand factor, insulin, proinsulin, specific insulin, apolipoprotein A-I (apo A-I), Lp(a), and leptin. Interaction analysis was also performed for tPA, apo A-I, Lp(a), leptin and proinsulin. RESULTS: Smoking, low plasma levels of apo A-I and high plasma levels of cholesterol, Lp(a), tPA, PAI-1, proinsulin and leptin were associated with myocardial infarction in univariate conditional logistic regression analysis. High tPA [odds ratio (OR), 21.3; 95% confidence interval (CI), 2.04-222] and Lp(a) (OR, 7.21; 95% CI, 1.31-39.8) and low apo A-I (OR, 0.15; 95% CI, 0.02-0.93) remained significant risk determinants in multivariate analysis with smoking habits, body mass index, hypertension, cholesterol, and diabetes included as covariates. There were non-significant synergic interactions between high Lp(a) and leptin and tPA, respectively, and between high Lp(a) and low apo A-I. CONCLUSION: Plasma levels of tPA, Lp(a), and apo A-I are independently associated with subsequent development of a first myocardial infarction in men.

Keyword
Apolipoproteins B/blood, Biological Markers/blood, Blood Pressure/physiology, Body Mass Index, Case-Control Studies, Diastole/physiology, Female, Fibrinolysis/*physiology, Humans, Leptin/*blood, Lipoprotein(a)/blood, Lipoproteins/*blood, Male, Middle Aged, Multivariate Analysis, Myocardial Infarction/*blood/*physiopathology, Plasminogen Activator Inhibitor 1/blood, Prospective Studies, Statistics, Sweden, Systole/physiology, Tissue Plasminogen Activator/blood, von Willebrand Factor/metabolism
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-13176 (URN)10.1097/01.hjr.0000116824.84388.a2 (DOI)15167204 (PubMedID)
Available from: 2007-11-23 Created: 2007-11-23 Last updated: 2017-12-14Bibliographically approved
4. Elevated plasma homocysteine: cause or consequence of myocardial infarction?
Open this publication in new window or tab >>Elevated plasma homocysteine: cause or consequence of myocardial infarction?
Show others...
2004 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 6, 491-498 p.Article in journal (Refereed) Published
Abstract [en]

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.

Keyword
Case-Control Studies, Creatinine/blood, Female, Homocysteine/*blood, Humans, Male, Middle Aged, Myocardial Infarction/*blood, Prospective Studies, Risk Factors, Serum Albumin/analysis, Smoking/adverse effects
Identifiers
urn:nbn:se:umu:diva-12981 (URN)10.1111/j.1365-2796.2004.01415.x (DOI)15554950 (PubMedID)
Available from: 2007-11-23 Created: 2007-11-23 Last updated: 2017-12-14Bibliographically approved

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CiteExportLink to record
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  • modern-language-association-8th-edition
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