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Management and Outcome in ST-Elevation Myocardial Infarction from a Gender Perspective
Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to evaluate baseline characteristics, management and outcome in real life ST-elevation myocardial infarction [STEMI] cohorts from a gender perspective. We aimed to evaluate the total STEMI population as well as certain subgroups, such as the youngest. Moreover we aimed to analyse gender differences in renal function, and the prognostic impact of reduced renal function in men and women with STEMI.

In Paper I all STEMI patients registered in RIKS-HIA between 1st Jan 1995 and 31st Dec 2006 were included, in total 54 146 patients, 35% women. Women were 7 years older than men, with 30 min longer median symptomto-door time. They had higher prevalence of co-morbidities such as diabetes, hypertension and heart failure whereas men were more often smokers, had a previous myocardial infarction [MI] or were previously revascularised. During hospital care, fewer women than men, 63% vs. 72%, p<0.001, received acute reperfusion therapy, odds ratio [OR] 0.83 (95% confidence interval [CI] 0.79 – 0.88) after multivariable adjustment. Inhospital mortality was 13% vs. 7%, women vs. men, p<0.001. After multivariable adjustments women had 22% higher risk of in-hospital death, OR 1.22 (95% CI 1.11 – 1.33). Adding reperfusion therapy to the adjustment model did not change the odds of death, OR 1.21 (1.11 – 1.32). Stratifying the cohort into four age-groups revealed increased mortality with increasing age as well as higher mortality in women than in men in all groups. The multivariable adjusted risk in women relative to men was highest amongst the youngest, OR 1.45 (95% CI 0.98 – 2.14). The long term prognosis was assessed in women vs. men with Cox proportional regression analyses, follow-up time 1 to 13 years. Women had 8% lower risk of long term mortality after multivariable adjustments, and after age-stratifying, women had better long term survival in all age-groups, except the youngest.

Previous studies based on mixed MI cohorts had found a gender-age interaction with higher risk of death women relative to men in the youngest group. In Paper II we included all STEMI patients <46 years old registered in RIKS-HIA between 1st Jan 1995 and 31st Dec 2006, 1748 men and 384 women. Cardiovascular risk factors were common, and women had more often clustering of risk factors compared to men. The most prevalent risk factor was smoking, 64% of the women compared to 58% of the men were current smokers. There was no gender difference in delay times or in rate of reperfusion. Almost 60% of both women and men underwent coronary angiography within one week. There was no gender difference in prevalence of non-obstructive disease, (p=0.64), but men had had multi-vessel/left main disease much more often than women (33.6% vs. 19.2%; p<0.001). In-hospital mortality was low, 3% in women vs. 1% in men, crude OR women vs. men 2.83 (95% CI 1.32 – 6.03). Female gender appeared as an independent predictor in the multivariable model of in-hospital mortality, OR 2.85 (95% CI 1.31– 6.19). When the cohort was followed up to 10 years (mean 5.4 years) the risk of mortality was not higher in women (hazard ratio [HR] 0.93, 95% CI 0.60 – 1.45; p=0.75), and men had significantly higher risk of a second new MI during the following 10 years, HR 1.82 (95% CI 1.25 – 2.65; p=0.002).

In the beginning of the 21st century there was a shift in reperfusion strategy with a decline in use of fibrinolytic therapy and an increase in use of primary PCI. We hypothesised that the gender differences noticed during the fibrinolytic era with lower chance of receiving reperfusion therapy and higher risk of early mortality in women, would have diminished during the new primary PCI era, as this is a better reperfusion strategy, especially for women. In Paper III we included STEMI patients from two time periods with different dominating reperfusion strategies in order to compare management and outcome between genders in both periods. Patients in the early period (n=15 697, 35% women) were registered in RIKS-HIA between 1st Jan 1998 and 31st Dec 2000 and those in the late period (n=14 380, 35% women) between 1st Jan 2004 and 31st Dec 2006. Among patients treated with reperfusion therapy 9% in the early compared to 68% in the late period were treated with primary PCI. The use of reperfusion therapy increased between the two periods, in men from 70.9% to 75.3%, in women from 63.1% to 63.6%. After multivariable adjustment, women were 14% and 20% less likely than men to receive reperfusion therapy, early and late periods, respectively. Heart failure, cardiogenic chock and major bleedings were more common in women compared to men. Evidence-based secondary preventive therapies were prescribed more often in the late compared to the early period in both genders, but more seldom to women in both periods. After multivariable adjustments women still had less chance of receiving ACE-inhibitors/ARBs but higher chance of receiving statins in the early period. In the late period women had 14 – 25% less chance of receiving any of the evidence-based secondary preventive therapies.

In Paper IV all consecutive patients who fulfilled the criteria for ST-elevation or bundle branch block on admission ECG and who were planned to undergo immediate coronary angiography with the intention to perform primary PCI at the Department of Cardiology in Linköping were included, 98 women and 176 men. Estimated glomerular filtration rate [eGFR] according to Modification of Diet in Renal Disease study [MDRD] was calculated for all patients and they were staged into CKD stages 1-5. Estimated GFR was lower in women than in men, mean eGFR 54 vs. 68 mL/min/1.73m2, p<0.001. Ten men but no woman were classified belonging to the best CKD stage 1(eGFR >90 mL/min/1.73m2). In total 67% of women compared to 27% of men were classified as having renal insufficiency [RI] (eGFR <60 mL/min/1.73m2) and female sex was a strong independent factor associated with RI, OR 5.06 (95% CI 2.66 – 9.59). Reduced eGFR per 10 mL/min decline was independently associated to higher risk of death and MACE (death, new MI or stroke) within one year in women whereas we found no such associations in men. There was a borderline significant interaction between gender and eGFR regarding one year mortality (p=0.08) but not regarding MACE (p=0.11).

As we found a remarkable gender difference in RI prevalence in Paper  IV, we analysed an updated SWEDEHEART database including the years since S-creatinine became a mandatory variable to register. In Paper V all STEMI patients registered between 1st of Jan 2003 and 31st of Dec 2009 were included, in total 37 991 patients (36% women). RI was present in 38% in women vs. 19% in men according to MDRD and in 50% of men vs. 22% of men according to Cockcroft Gault [CG] (p<0.001 for both comparisons). Female gender was independently associated with RI regardless of used formula. In both genders, RI patients were older, had higher co-morbidity, suffered from more complications and had lower chance of receiving reperfusion therapy and evidence-based therapy at discharge compared to non RI patients. Among both RI and non RI patients, men had significantly higher chance than women of getting these therapies. In-hospital mortality was four to five times higher in RI vs. non RI patients. RI compared to non RI patients had approximately doubled risk of inhospital mortality in women and 2.5 times higher risk in men after multivariable adjustment. Regardless of used formula, the risk of dying at hospital increased with approximately 30% and the risk of long term mortality with approximately 10% in both genders per 10 mL/min decline of eGFR. There was no significant interaction between gender and eGFR regarding short- or long term outcome according to any of the formulas. Women had twice as high in-hospital and also higher cumulative long term mortality than men. After multivariable adjustments including all confounders except kidney function women had 7% lower risk of long term mortality but still 11% higher risk of in-hospital mortality. If eGFR according to any of the formulas was also included, there was no longer a gender difference regarding in-hospital mortality and women had lower risk of long term mortality. This was also the case if only adjusting for eGFR according to CG.

Conclusion: In the real life STEMI setting, women were older with higher co-morbidity, longer delay, more complications and twice as high in-hospital mortality. They had significantly less chance of receiving acute reperfusion therapy, also after adjusting for possible confounders. During the fibrinolytic era women had higher risk of severe bleedings. We hypothesised that the gap in management would have decreased during the new primary PCI era, with a less time-dependent regime with less risk of fatal complications. Our hypothesis failed, and future studies ought to further scrutinise this gender difference in management. The less chance of reperfusion therapy did anyhow not explain the higher in-hospital mortality in women, which was 10-20% higher after multivariable adjustments, consistent with previous findings. Moderate to severe chronic kidney disease was very common in women with STEMI, 50% according to the Cockcroft Gault formula. Estimated GFR has seldom been taken into account in studies evaluating gender differences in outcome. If adjustment for eGFR was done, alone or added to the all other co-variates, women had no longer higher risk of in-hospital mortality. Adjusted long term outcome was better in women than in men, which was also the case in the youngest cohort when studied separately.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2012. , 100 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1276
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-73916ISBN: 978-91-7393-024-6 (print)OAI: oai:DiVA.org:liu-73916DiVA: diva2:478631
Public defence
2012-02-10, Berzeliussalen, Universitetssjukhuset, Campus US, Linköpings Universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-01-16 Created: 2012-01-16 Last updated: 2013-09-11Bibliographically approved
List of papers
1. A gender perspective on short- and long term mortality in ST-elevation myocardial infarction: a report from the SWEDEHEART register
Open this publication in new window or tab >>A gender perspective on short- and long term mortality in ST-elevation myocardial infarction: a report from the SWEDEHEART register
2013 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 18, no 2, 1041-1047 p.Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies of patients admitted for ST-elevation myocardial infarction [STEMI] have indicated that women have a higher risk of early mortality than do men. These studies have presented limited information on gender related differences in the short term and almost no information on the long term. Methods and results: We analysed a prospective, consecutively included STEMI population consisting of 54,146 patients (35% women). This population consists of almost all patients hospitalised in Sweden between January 1, 1995 and December 31, 2006 as recorded in the SWEDEHEART register (formerly RIKS-HIA). Follow-up time ranged from one to 13 years (mean 4.6). Women had a lower probability of being given reperfusion therapy, odds ratio [OR] 0.83 (95% confidence interval [CI] 0.79-0.88). During the time these STEMI patients were in the hospital, 13% of the women and 7% of men died, multivariable adjusted OR 1.21 (95% CI 1.11-1.32). During the follow up period, 46% of the women died as compared with 32% of the men. There was, however, no gender difference in age-adjusted risk of long term mortality (hazard ratio [HR] 0.98, 95% CI 0.95-1.01) whereas the multivariable adjusted risk was lower in women (HR 0.92, 95% CI 0.89-0.96). The long term risk of re-infarction was the same in men and women (HR 0.98, 95% CI 0.93-1.03) whereas men in the youngest group had a higher risk than women in that age group (HR 0.82, 95% CI 0.72-0.94). Conclusion: In STEMI, women had a higher risk of in-hospital mortality but the long-term risk of death was higher in men. More studies are needed in the primary percutaneous coronary intervention (pPCI) era that are designed to determine why women fare worse than men after STEMI during the first phase when they are in hospital

Place, publisher, year, edition, pages
Elsevier Ireland Ltd, 2013
Keyword
Myocardial infarction, prognosis, in-hospital mortality, sex factors
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-73912 (URN)10.1016/j.ijcard.2012.10.028 (DOI)000325412800084 ()
Available from: 2012-01-16 Created: 2012-01-16 Last updated: 2017-12-08Bibliographically approved
2. Gender perspective on risk factors, coronary lesions and long-term outcome in young patients with ST-elevation myocardial infarction
Open this publication in new window or tab >>Gender perspective on risk factors, coronary lesions and long-term outcome in young patients with ST-elevation myocardial infarction
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2010 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 96, no 6, 453-459 p.Article in journal (Refereed) Published
Abstract [en]

Objective Previous data on young patients with acute coronary syndrome (ACS) have indicated higher rates of normal coronary angiograms but higher mortality in women than men. However, ST-elevation myocardial infarction (STEMI) differs from non-ST-elevation ACS in many aspects. We elucidated sex differences in risk factors, angiographic findings and outcome in consecutive STEMI patients below 46 years of age. Design Retrospective cohort study. Setting The Swedish registers for CCU care and coronary angioplasty; RIKS-HIA and SCAAR. Patients 2132 STEMI patients below 46 years of age admitted to intensive coronary care units in Sweden between 1995 and 2006 and followed for at least 1 year. Main outcome measures Angiographic findings and short-term and long-term mortality. Results Risk factors were more common in women. Significant coronary lesions were equally common (92.1% vs 93.1%, p=0.64) while single vessel disease was more common (72.9% vs 59.3%; pandlt;0.001) in women. Women had higher multivariable adjusted in-hospital mortality, OR 2.85 (95% CI 1.31 to 6.19) while long-term mortality was the same, HR 0.93 (95% CI 0.60 to 1.45). The catch-up of mortality in men might be related to a higher occurrence of re-infarctions, HR 1.82 (95% CI 1.25 to 2.65). Conclusions STEMI below age 46 is a more rare condition in women than in men and more often related to cardiovascular risk factors. More than 90% of both men and women had coronary lesions, in women more often single vessel lesions. Female sex is associated with higher in-hospital mortality, while long-term mortality is low without difference between genders.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-54707 (URN)10.1136/hrt.2009.175463 (DOI)000275727700009 ()
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2017-12-12Bibliographically approved
3. Time trends in STEMI—improved treatment and outcome but still a gender gap: a prospective observational cohort study from the SWEDEHEART register
Open this publication in new window or tab >>Time trends in STEMI—improved treatment and outcome but still a gender gap: a prospective observational cohort study from the SWEDEHEART register
2012 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 2Article in journal (Refereed) Published
Abstract [en]

Objective In ST elevation myocardial infarction women received less evidence-based medicine and had worse outcome during the fibrinolytic era. With the shift to primary percutaneous coronary intervention (pPCI) as preferred reperfusion strategy, the authors aimed to investigate whether these gender differences has diminished.

Design, setting and participants Cohort study including consecutive ST elevation myocardial infarction patients registered 1998–2000 (n=15 697) and 2004–2006 (n=14 380) in the Register of Information and Knowledge about Swedish Heart Intensive care Admissions.

Outcome measures 1. Use of evidence-based medicine such as reperfusion therapy (pPCI or fibrinolysis) and evidence-based drugs at discharge. 2. Inhospital and 1-year mortality.

Results Of those who got reperfusion therapy, pPCI was the choice in 9% in the early period compared with 68% in the late period. In the early period, reperfusion therapy was given to 63% of women versus 71% of men, p<0.001. Corresponding figures in the late period were 64% vs 75%, p<0.001. After multivariable adjustments, the ORs (women vs men) were 0.86 (95% CI 0.78 to 0.94) in the early and 0.80 (95% CI 0.73 to 0.89) in the late period. As regards evidence-based secondary preventive drugs at discharge in hospital survivors (platelet inhibitors, statins, ACE inhibitors/angiotensin receptor blockers and β-blockers), there were small gender differences in the early period. In the late period, women had 14%–25% less chance of receiving these drugs, OR 0.75 (95% CI 0.68 to 0.81) through 0.86 (95% CI 0.73 to 1.00). In both periods, multivariable-adjusted inhospital mortality was higher in women, OR 1.18 (95% CI 1.02 to 1.36) and 1.21 (1.00 to 1.46). One-year mortality was gender equal, HR 0.95 (95% CI 0.87 to 1.05) and 0.96 (0.86 to 1.08), after adding evidence-based medicine to the multivariable adjustments.

Conclusion In spite of an intense gender debate, focus on guideline adherence and the change in reperfusion strategy, the last decade gender differences in use of reperfusion therapy and evidence-based therapy at discharge did not decline during the study period, rather the opposite. Moreover, higher mortality in women persisted.

Keyword
ST-elevation myocardial infarction, sex factors, reperfusion therapy, mortality, evidence-based medicine
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-73914 (URN)10.1136/bmjopen-2011-000726 (DOI)000315042100057 ()
Available from: 2012-01-16 Created: 2012-01-16 Last updated: 2017-12-08Bibliographically approved
4. Gender difference in prevalence and prognostic impact of renal insufficiency in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention
Open this publication in new window or tab >>Gender difference in prevalence and prognostic impact of renal insufficiency in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention
Show others...
2011 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 97, no 4, 308-314 p.Article in journal (Refereed) Published
Abstract [en]

Objective To evaluate if female gender is associated with renal insufficiency in patients with ST-elevation myocardial infarction (STEMI) and if there is a gender difference in the prognostic importance of renal insufficiency in STEMI. Design Single-centre observational study. Setting One tertiary cardiac centre. Patients All consecutive patients with STEMI planned for primary percutaneous coronary intervention in one Swedish county in 2005 (98 women and 176 men). Main outcome measures Logistic regression analyses were conducted to evaluate the predictors of renal insufficiency, associations between estimated glomerular filtration rate (eGFR) and outcome in each gender and a possible interaction between gender and eGFR regarding outcome. Results Renal insufficiency was defined as eGFR less than 60 ml/min per 1.73 m(2). 67% of women had renal insufficiency compared with 26% of men, OR 5.06 (95% CI 2.66 to 9.59) after multivariable adjustment. In women each 10 ml/min per 1.73 m 2 increment of eGFR was associated with a 63% risk reduction for 1-year mortality, OR 0.37 (95% CI 0.15 to 0.89). No such association was found in men, OR 1.05 (95% CI 0.63 to 1.76). A trend towards a significant interaction between gender and eGFR regarding 1-year mortality was found, OR 2.05 (95% CI 0.93 to 4.50). Conclusions A considerable gender difference in the prevalence of renal insufficiency in STEMI was found and renal insufficiency seemed to be a more important prognostic marker in women. These results are important as previous STEMI studies have shown higher multivariable adjusted mortality in women than in men but renal function has seldom been taken into consideration.

Place, publisher, year, edition, pages
BMJ Publishing Group; 1999, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-65947 (URN)10.1136/hrt.2010.194282 (DOI)000286459400008 ()
Note
Original Publication: Sofia Lawesson, Tim Tödt, Joakim Alfredsson, Magnus Janzon, Ulf Stenestrand and Eva Swahn, Gender difference in prevalence and prognostic impact of renal insufficiency in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention, 2011, HEART, (97), 4, 308-314. http://dx.doi.org/10.1136/hrt.2010.194282 Copyright: BMJ Publishing Group; 1999 http://group.bmj.com/ Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2017-12-11Bibliographically approved
5. Prevalence and prognostic impact of renal insufficiency in STEMI from a gender perspective: data from a large prospective cohort
Open this publication in new window or tab >>Prevalence and prognostic impact of renal insufficiency in STEMI from a gender perspective: data from a large prospective cohort
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Data indicate that female gender may be associated with increased risk of RI in MI but also that presence of RI has higher prognostic impact in women. In case of ST-elevation MI [STEMI], women have higher adjusted mortality compared to men but RI has seldom been taken into account.

Methods and Results: All STEMI patients registered in the Swedish national quality register SWEDEHEART between 2003 and 2009 were included (37991 patients, 66% men). Based on s-creatinine on admission, glomerular filtration rate [GFR] was estimated according to MDRD and Cockcroft-Gault [CG]. RI was defined as eGFR below 60 mL/min. Women had 1.6-2.2 times higher multivariable adjusted risk of RI and half of all women had RI according to CG. RI was associated with 2-2.5 times higher risk of in-hospital and approximately 1.5 times higher risk of long-term mortality in both genders. Each 10 mL/min decline of eGFR was associated with 22-33% and 9-16% increased risk of in-hospital and. long-term mortality, respectively. There was no significant interaction between gender and eGFR regarding outcome. Both in-hospital and long-term mortality was twice as high in women but after adjusting for eGFR according to CG, there was no longer any gender difference in early outcome and long term outcome was better in women.

Conclusions: Among STEMI patients

1) Female sex was independently associated with RI

2) Reduced eGFR regardless of used formula was a strong independent risk factor for mortality without a significant gender difference in prognostic impact.

3) Reduced eGFR (according to CG) appeared to be a main explanatory variable to the higher mortality in women.

Keyword
Gender differences in prevalence and prognostic impact of renal insufficiency in STEMI Address for correspondence: Sofia Sederholm Lawesson, M.D. Department of Medical and Health Sciences, Division of Cardiovascular Medicine Linköping University SE-581 85 Linköping SWEDEN Telephone: +46 101032169 Fax: +46 101032171 Email: sofia.
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-73915 (URN)
Available from: 2012-01-16 Created: 2012-01-16 Last updated: 2013-09-11Bibliographically approved

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