Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Different quantitative apoptotic traits in coronary atherosclerotic plaques from patients with stable angina pectoris and acute coronary syndromes.

BACKGROUND: Apoptosis in human atherosclerotic coronary plaques possibly causes plaque destabilization by contributing to the weakening and breaking down of the fibrous cap. We tested the hypothesis that apoptosis is quantitatively increased in unstable atherosclerotic plaques. METHODS AND RESULTS: We analyzed the expression of apoptotic genes such as BAX, CASP1, FAS, FAS L, FOS, MDM2, NFkB2, P53, PCNA, TERT, and XRCC1 in coronary plaques collected with directional coronary atherectomy from 15 patients with stable angina and 15 with acute coronary syndromes without ST elevation (ACS). Total RNA was extracted and cDNA was amplified with a specific set of primers and TaqMan probes. Apoptosis was also revealed by DNA laddering. To clarify the source of mRNAs, we performed in situ reverse transcriptase-polymerase chain reaction coupled with immunocytochemistry and found a substantial overlap between the mRNAs of the above genes and vascular smooth muscle cells. Gene expression analysis showed that the proapoptotic genes (ie, BAX, CASP1, FAS, FAS L, FOS, NFkB2, P53, PCNA) were significantly more expressed (P<0.001) in ACS plaques, whereas the antiapoptotic genes (ie, MDM2, TERT, XRCC1) were more transcribed (P<0.001) in stable angina plaques. Total gDNA gel electrophoresis identified a laddering pattern in the ACS plaques as evidence of end-point apoptosis. Western blotting substantially confirmed the above data. CONCLUSIONS: Our findings support the idea that ACS plaques are committed to apoptosis through an established meshwork of gene activation and inactivation, whereas stable angina plaques retain active cell homeostasis and repair mechanisms.

Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction.

Thrombolytic therapy activates the contact system, and factor XII activation may activate the coagulation cascade and inflammation. It is not known whether an early inflammatory response is induced by thrombolytic therapy in patients with acute myocardial infarction (AMI). We prospectively measured the plasma levels of activated factor XII, cleaved kininogen, prothrombin fragment 1 + 2 (as indexes of the contact phase and coagulation activation), and interleukin-6 and C-reactive protein (CRP) (as indexes of inflammation) in 39 patients hospitalized for AMI within 12 hours of symptom onset: 26 receiving thrombolytic therapy and 13 heparin alone. Blood samples were collected at baseline and after 90 minutes and 24 hours. Patients undergoing thrombolysis had a significant early increase in activated factor XII (from 2.2 ng/ml at baseline to 4.7 ng/ml after 90 minutes; p = 0.0001), cleaved kininogen (from 26% to 37%; p = 0.001), and fragment 1 + 2 (from 1.4 to 2.1 nmol/L; p = 0.0001), whereas the 24-hour levels were similar to baseline levels. The levels of interleukin-6 significantly increased during the first 90 minutes (from 3.9 to 6.3 microg/ml; p = 0.001), and were even higher after 24 hours (11.9 ng/ml, p = 0.0001). CRP levels increased only after 24 hours (p = 0.0001). There were no changes in these parameters in patients receiving heparin alone, except for a 24-hour increase in interleukin-6 and CRP levels. Thus, in patients with AMI receiving thrombolytic therapy, early activation of inflammation parallels the activation of the contact system and the coagulation cascade, which might contribute to microvascular obstruction and reperfusion injury.

Dobutamine-induced ST-segment elevation associated with a biphasic response of wall motion in patients with a recent myocardial infarction is caused by myocardial ischaemia and is abolished by revascularization of the infarct-related artery.

OBJECTIVE: ST-segment elevation is frequently induced by dobutamine in patients with a recent myocardial infarction and may represent dyskinesia of the infarcted region or myocardial viability and ischaemia. Revascularization of the infarct-related artery may abolish myocardial ischaemia, and thus represents a useful tool to verify the significance of this finding. The aim of this study was to assess the relation between ST-segment elevation and wall motion response during dobutamine echo stress test and to evaluate the effect of coronary revascularization with percutaneous coronary angioplasty of the infarct-related artery on stress test results. METHODS AND RESULTS: Twenty-two patients (17 men; mean age 58+/-12 years) with a first acute myocardial infarction (5 anterior (23%) and 17 (77%) inferior) who showed ST-segment elevation during a dobutamine echo stress test performed early (7+/-5 days) after the acute event where included in the analysis. All patients underwent coronary arteriography followed by percutaneous revascularization with coronary angioplasty or atherectomy with or without stenting of the culprit lesion and a second dobutamine echo stress test at a mean of 40+/-20 days after revascularization. The minimal lumen diameter increased from 0.63+/-0.36 to 3+/-0.44 mm and % diameter stenosis decreased from 80+/-11 to 12+/-7 after revascularization. At baseline evaluation there were 62 normal moving segments (34%), 57 (32%) akinetic and 62 (34%) hypokinetic segments within the area at risk. Maximal ST-segment shift changed from a basal mean value of 0.41+/-0.6 to a peak value of 2.15+/-0.9 mm; angina developed in 6/22 patients (22%). A biphasic response to dobutamine indicative of myocardial ischaemia within the infarcted area was observed in 20/22 patients (91%) and in 54/74 (73%) segments showing wall motion abnormalities. After revascularization of the infarct-related artery 78 (43%) segments were considered to be normal, 46 (25%) akinetic and 57 (32%) hypokinetic. Dobutamine-induced ST-segment elevation in 6/22 cases (27%), but the amount of ST-segment shift at peak stress was significantly reduced (from 2.15+/-0.9 to 0.30+/-0.5 mm) and angina was present in 1 patient only (5%) despite a significant increase of double product compared to the pre-revascularization test (from 17,348+/-3536 to 21,005+/-4105, p < 0.003). At echocardiographic analysis, ischaemia involved only 4 segments (2%), 3 of them showing the persistence of a biphasic response to dobutamine. CONCLUSIONS: In patients with a recent myocardial infarction and no baseline dyskinesia dobutamine-induced ST-segment elevation in the infarct-related leads is usually associated with a biphasic response of wall motion within the infarcted region and may be considered an ancillary sign of myocardial ischaemia because it is abolished in the great majority of cases by successful revascularization of the infarct-related artery.

ATPases enzyme activities during ageing in different types of somatic and synaptic plasma membranes from rat frontal cerebral cortex.

The catalytic properties of energy-utilizing ATPases enzyme systems related to ions homeostasis were evaluated in different types of synaptic plasma membranes (SPM) and in somatic plasma membranes (SM) from cerebral cortex of rats aged 5, 10, and 22 months. The following enzymes were evaluated: Na+, K+-ATPase, Ca2+, Mg2+-ATPase, Mg2+-ATPase and the activity of acetylcholine esterase (AChE) was also evaluated. The ATPases located on SM and SPM and synaptic vesicles are involved in the regulation of presynaptic nerve ending homeostasis and postsynaptic activities. Different types of SM and SPM (three types) were obtained by combinations of differential and density gradient ultracentrifugation techniques in sucrose-Ficoll media: the first was obtained by purification of the sediment of mitochondrial supernate and the second after synaptosomal lysis and purification on density gradient. In the cerebral cortex of 5-month-old rats, the catalytic properties of ATPases systems markedly differ according to the different types of SPM and SM, thus indicating that the metabolic role of each ATPase is determined by their subcellular in vivo localization. As regards ageing: (i) ATPase enzyme catalytic activities tend to decrease during ageing in a complex way; (ii) ageing induced specific modifications in individual ATPases according to their subsynaptic localization; and (iii) these effects are probably due to specific biochemical situations that take place at each age, reflecting the bioenergetic state of the cerebral tissue with respect to the energy demand. The cerebral concentration and content of SM proteins were increased by ageing suggesting that many defective noncatalytic proteins may be formed during ageing, as shown by immunoblotting techniques.