Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry

Alabas, Oras; Gale, Chris P; Hall, Marlous; Rutherford, Mark J.; Szummer, Karolina; Lawesson, Sofia Sederholm; Alfredsson, Joakim; Lindahl, Bertil; Jernberg, Tomas

doi:10.1161/jaha.117.007123

Cited by 156 publications

(140 citation statements)

References 43 publications

(70 reference statements)

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“…Myocardial function and the ability to withstand ischemic insult may also differ in women compared to men (11)(12)(13)(14). Women who present with acute and chronic cardiovascular diseases remain under-studied and, therefore, are likely under-treated (15). The clinical presentation, management, and response to therapies for MI may also be different in women compared to men (16,17).…”

Section: Introductionmentioning

confidence: 99%

A Sex-Specific Switch in Platelet Receptor Signaling Following Myocardial Infarction

Kim

Auerbach

Sadhra

et al. 2019

Preprint

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Word Count: abstract 244 (abstract), 3639 (main) ABSTRACT BACKGROUND: A Sex-specific, personalized approach to anti-platelet therapy may be important in patients with myocardial infarction (MI). OBJECTIVES:Our goal was to determine whether platelets activate differently in healthy men and women compared to following MI. METHODS:Blood was obtained from healthy subjects or patients presenting acutely with STsegment Elevation Myocardial Infarction (STEMI) and non-ST Segment Elevation Myocardial Infarction (NSTEMI). Platelet function through surface receptor activation was examined in healthy subjects, in patients with MI, and in age-and strain-matched mice before and after MI.Multivariate regression analyses revealed clinical variables associated with platelet receptor sensitivity at the time of MI. RESULTS:Platelets from healthy women are dose-dependently more active compared to men, particularly through the platelet thromboxane signaling pathway (7.8-fold increase in women vs.3.0-fold in men, P=0.02). At the time of MI, platelet activation through surface proteaseactivated receptor 1 (PAR1) was less in women than men (3.5-fold vs. 8.5-fold, respectively, P=0.0001). Multivariate regression analyses revealed male sex (P=0.04) and NSTEMI (P=0.003) as independent predictors of enhanced platelet PAR1 signaling at the time of MI. Similar to humans, healthy female mice showed preferential thrombin-mediated platelet activation compared to male mice (8.7-fold vs. 4.8-fold, respectively; P<0.001). In the immediate post-MI environment, male mice showed preferential thrombin-mediated platelet activation compared to female mice (12.4-fold vs. 5.5-fold, respectively; P<0.001).3 CONCLUSIONS: These results outline a previously unrecognized sex-dependent platelet phenotype where inhibition of thrombin signaling in the peri-MI environment-particularly in males-may be an important consideration. CONDENSED ABSTRACTPreclinical studies evaluating anti-platelet drugs are generally conducted in platelets isolated from healthy individuals. Growing evidence suggests changes in platelet signaling properties in certain disease conditions compared to healthy platelets may alter the response to anti-platelet medications. This investigation revealed that platelets from men and women who are healthy and following MI signal differently, particularly through thromboxane and PAR1 receptors. This effect was especially noted in patients with NSTEMI compared to STEMI. These observations raise the possibility of considering a sex-specific anti-platelet regimen for males and females in atheroembolic vascular diseases such as NSTEMI..

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Section: Introductionmentioning

confidence: 99%

A Sex-Specific Switch in Platelet Receptor Signaling Following Myocardial Infarction

Kim

Auerbach

Sadhra

et al. 2019

Preprint

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“…5,6 Nýleg saensk rannsókn sýndi þó að konur hlutu síður meðferð samkvaemt klínískum leiðbeiningum, baeði hvað varðar lyfjameðferð og inngrip. 7 Engin íslensk rannsókn hefur borið saman meðferð kransaeða-sjúkdóms með hjáveituaðgerð milli kynja. Þótt konur séu yfirleitt um fjórðungur þessara sjúklinga hefur árangur aðgerðarinnar hjá konum lítið verið rannsakaður.…”

Section: Inngangurunclassified

Árangur kransæðahjáveituaðgerða hjá konum á Íslandi

Gardarsdóttir

Arnadottir

Aðalsteinsson

et al. 2018

LBL

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ur innan 30 daga frá opinni hjartaaðgerð en þar er kvenkyn sér-stakur áhaettuþáttur. 15 Þaer fáu rannsóknir sem hafa borið saman langtímalifun milli kynja eftir kransaeðahjáveitu hafa í flestum tilvikum sýnt lakari horfur kvenna. 8,16,17 Rannsóknum virðist þó ekki bera saman um hvort kvenkyn sé sjálfstaeður áhaettuþáttur síðri lifunar eftir kransaeðahjáveitu, enda þótt nýleg safngreining á 20 rannsóknum hafi bent til þess. 16 Árangur kransaeðahjáveituaðgerða á Íslandi hefur töluvert verið rannsakaður á síðustu árum og hafa vísindagreinar verið birtar úr þessum efnivið. Meðal annars hafa undirhópar sjúklinga, eins og aldraðir, sykursjúkir og sjúklingar sem þjást af offitu, verið teknir fyrir en einnig birtist nýlega rannsókn um langtímaárangur eftir kransaeðahjáveitu. [18][19][20][21] Árangur kransaeðahjáveituaðgerðahjá konum á Íslandi Á G R I P InngangurMarkmið þessarar rannsóknar var að bera saman árangur kransaeða-hjáveituaðgerða hjá konum og körlum á Íslandi með áherslu á snemmog síðkomna fylgikvilla, 30 daga dánartíðni og langtímalifun. Efniviður og aðferðirAfturskyggn rannsókn á öllum sjúklingum sem gengust undir kransaeðahjáveituaðgerð á Íslandi á árunum 2001-2013. Upplýsingar fengust úr sjúkraskrám og Dánarmeinaskrá Embaettis landlaeknis. Fylgikvillum var skipt í snemm-og síðkomna fylgikvilla og heildarlifun reiknuð með aðferð Kaplan-Meier. Fjölþátta aðhvarfsgreining var notuð til að meta forspárþaetti dauða innan 30 daga og Cox aðhvarfs-greining til að meta forspárþaetti verri langtímalifunar. Meðaleftirfylgd var 6,8 ár. NiðurstöðurAf 1755 sjúklingum voru 318 konur (18%). Meðalaldur þeirra var fjórum árum haerri en karla (69 ár á móti 65 árum, p<0,001), þaer höfðu oftar sögu um háþrýsting (72% á móti 64%, p=0,009) og EuroSCOREst þeirra var haerra (6,1 á móti 4,3, p<0,001). Hlutfall annarra áhaettu-þátta eins og sykursýki var hins vegar sambaerilegt, líkt og útbreiðsla kransaeðasjúkdóms. Alls létust 12 konur (4%) og 30 karlar (2%) innan 30 daga frá aðgerð en munurinn var ekki marktaekur (p=0,08). Tíðni snemmkominna fylgikvilla, baeði minniháttar (53% á móti 48% p=0,07) og alvarlegra (13% á móti 11%, p=0,2), var sambaerileg. Fimm árum frá aðgerð var lifun kvenna 87% borin saman við 90% hjá körlum (p=0,09). Þá var tíðni síðkominna fylgikvilla sambaerileg hjá konum og körlum 5 árum frá aðgerð (21% á móti 19%, p=0,3). Kvenkyn reyndist hvorki sjálfstaeður forspárþáttur 30 daga dánartíðni (OR 0,99; 95%-ÖB: 0,97-1,01) né verri lifunar (HR 1,08; 95%-ÖB: 0,82-1,42). ÁlyktunMun faerri konur en karlar gangast undir kransaeðahjáveituaðgerð á Íslandi og eru þaer fjórum árum eldri þegar kemur að aðgerð. Árangur kransaeðahjáveitu er góður hjá konum líkt og körlum, en 5 árum eftir aðgerð eru 87% kvenna á lífi. InngangurKransaeðasjúkdómur er ein helsta dánarorsök Íslendinga, baeði kvenna og karla. 1 Fyrir tíðahvörf er tíðni kransaeðasjúkdóms laegri meðal kvenna og þaer eru að jafnaði allt að áratug eldri en karlar þegar þaer greinast með sjúkdóminn.2 Ástaeðan fyrir þessum mun er ekki að öllu leyti þekkt en er helst rakin...

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“…They have been used, eg, in the international comparisons of cancer survival between countries, between regions within a country, or between other population subgroups . The same methods apply to the assessments of mortality associated with diseases other than cancer, too, eg, cardiovascular and cerebrovascular diseases and HIV …”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] They have been used, eg, in the international comparisons of cancer survival between countries, 5,6 between regions within a country, 7,8 or between other population subgroups. 9 The same methods apply to the assessments of mortality associated with diseases other than cancer, too, eg, cardiovascular 10,11 and cerebrovascular diseases 12 and HIV. 13 Excess mortality is often modeled by splitting follow-up time in prespecified intervals within which binomial distribution for the number of deaths 14 or a piecewise constant excess hazard 2 is assumed.…”

Section: Introductionmentioning

confidence: 99%

Estimating multilevel regional variation in excess mortality of cancer patients using integrated nested Laplace approximation

Seppä

Rue

Hakulinen

et al. 2018

Statistics in Medicine

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Models of excess mortality with random effects were used to estimate regional variation in relative or net survival of cancer patients. Statistical inference for these models based on the Markov chain Monte Carlo (MCMC) methods is computationally intensive and, therefore, not feasible for routine analyses of cancer register data. This study assessed the performance of the integrated nested Laplace approximation (INLA) in monitoring regional variation in cancer survival. Poisson regression model of excess mortality including both spatially correlated and unstructured random effects was fitted to the data of patients diagnosed with ovarian and breast cancer in Finland during 1955‐2014 with follow up from 1960 through 2014 by using the period approach with five‐year calendar time windows. We estimated standard deviations associated with variation (i) between hospital districts and (ii) between municipalities within hospital districts. Posterior estimates based on the INLA approach were compared to those based on the MCMC simulation. The estimates of the variation parameters were similar between the two approaches. Variation within hospital districts dominated in the total variation between municipalities. In 2000‐2014, the proportion of the average variation within hospital districts was 68% (95% posterior interval: 35%‐93%) and 82% (60%‐98%) out of the total variation in ovarian and breast cancer, respectively. In the estimation of regional variation, the INLA approach was accurate, fast, and easy to implement by using the R‐INLA package.

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Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry

Cited by 156 publications

References 43 publications

A Sex-Specific Switch in Platelet Receptor Signaling Following Myocardial Infarction

A Sex-Specific Switch in Platelet Receptor Signaling Following Myocardial Infarction

Árangur kransæðahjáveituaðgerða hjá konum á Íslandi

Estimating multilevel regional variation in excess mortality of cancer patients using integrated nested Laplace approximation

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