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- Stenestrand, Ulf, 1961-
(författare)
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Improving outcome in acute myocardial infarction
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Despite common guidelines there are vanatlons in the treatment of acute myocardial infarction (AMI) between hospitals in Sweden. Uncertainties remain regarding the efficacy of early statin therapy and early revascularisation in AMI patients. In the elderly patients also the role of fibrinolytic therapy has been questioned.Methods: We created a national quality assurance register named RIKS-HIA including all patients admitted to participating hospitals' ICCU. The database accumulates information about baseline characteristics, interventions, complications and outcome in consecutive patients. The merging of the database with the Cause of Death Register provides opportunity to compare the effects of treatments on long-term outcome. Multivariate Cox regression analysis and propensity score was used to evaluate outcome in AMI patients of the studied interventions, and to compare activity level between different hospitals.Results: After patient characteristics were taken into account there were still significant differences between the hospitals in some treatment modalities that remained over time. There was no correlation between hospital size and activity level. In 19 599 in-hospital survivors after their first registry-recorded AMI at an age below 80 years early statin treatment was associated with a 25 % relative risk reduction of I-year mortality. In 21 912 patients with first registry-recorded AMI younger than 80 years and alive at day 14, early revascularisation was associated with a 50 % relative reduction of I-year mortality. For both therapies the effects were homogeneous among all subgroups based on age, gender, baseline characteristics, previous disease manifestations and medication. Fibrinolytic therapy in ST-segment elevation myocardial infarction patients 75 years of age and older showed a net benefit of 13% in outcome when non-fatal intracranial haemorrhage and I-year survival were analysed.Conclusion: The results indicates the need of continuous quality assurance, and strategies to reduce the differences in AMI therapy between hospitals. They lend support to early statin and early revascularisation regimens in AMI patients. Fibrinolytic therapy is recommended also in the elderly patients.
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| 2. |
- Söderberg, Stefan, 1957-
(författare)
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Leptin : a risk marker for cardiovascular disease
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A major cause of morbidity and early death in the Western societies is cardiovascular disease (CVD) secondary to atherosclerotic disease. Metabolic aberrations have been linked to CVD. Particular combinations of these so-called risk markers are common and (central) obesity, Type 2 diabetes, impaired glucose tolerance, hypertension, dyslipidemia, dysfibrinolysis and hyperinsulinemia are often associated. This has been entitled the Insulin Resistance Syndrome (1RS), due to underlying insulin resistance. Moreover, aberrations in circulating levels of androgens and IGF-binding proteins are associated with 1RS.The main hypothesis in this thesis was that increased levels of leptin, the recently discovered adipocyte derived hormone in combination with obesity may be an important factor in the link between 1RS and the development of CVD.The association between leptin levels and variables associated with the Insulin Resistance Syndrome was studied in a healthy sample (n=163) of middle-aged men and women from the northern Sweden MONICA health survey. Central obesity was associated with high levels of leptin and insulin in men and women. In contrast, central obesity was linked to low testosterone levels in men, whereas in women, central obesity was associated with high testosterone but low SHBG levels. Furthermore, in males and postmenopausal women central obesity was a major determinant for circulating leptin. Leptin levels were associated with biochemical androgenicity in non-obese men and women. The direction of this association was dependent on gender and body fat distribution. Specifically, testosterone was inversely associated to leptin in non-obese men and in normal weight women whereas testosterone was positively associated to leptin in non-obese women. In contrast, adiposity and insulin levels, but not testosterone, were associated to leptin in obese men and women. Similarly, leptin was associated to IGFBP-1 and proinsulin in non-obese men and premenopausal women. Hyperleptinemia was significantly associated to high PAI-1 levels in men and in centrally obese women. In a multivariate model, high leptin levels predicted PAI-1 levels in men but not in women. Finally, leptin levels were related to blood pressure in obese men.The impact of hyperleptinemia on future risk for development of CVD was tested in a nested case-referent study based on the MONICA and the Västerbotten Intervention Program surveys. It was found that hyperleptinemia and high total cholesterol levels were associated with increased risk for development of myocardial infarction whereas high levels of apolipoprotein A-l were protective. Hyperleptinemia together with hypertension remained as significant risk markers for hemorrhagic stroke whereas hypertension alone predicted ischemic stroke. The combinations of hyperleptinemia on one hand and low apolipoprotein A- 1 and high blood pressure on the other were associated with a pronounced increased risk for myocardial infarction and hemorrhagic stroke, respectively.In conclusion, hyperleptinemia is independently associated with several risk markers for CVD included in the insulin resistance syndrome. Furthermore, high leptin levels predict the development of CVD.
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