Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction.

Non-infarcted myocardium after coronary occlusion undergoes progressive morphological and functional changes. The purpose of this study was to determine whether non-infarcted myocardium exhibits (1) alteration of the substrate pattern of myocardial metabolism and (2) concomitant changes in the expression of regulatory proteins of glucose and fatty acid metabolism. Myocardial infarction was induced in rats by ligation of the left coronary artery. One day and eight weeks after coronary occlusion, glucose and palmitate oxidation were measured. Expression of selected proteins of metabolism were determined one day to 12 weeks after infarction. One day after coronary occlusion no difference of glucose and palmitate oxidation was detectable, whereas after eight weeks, glucose oxidation was increased (+84%, P<0.05) and palmitate oxidation did not change significantly (-19%, P=0.07) in infarct-containing hearts, compared with hearts from sham-operated rats. One day after coronary occlusion, myocardial mRNA expression of the glucose transporter GLUT-1 was increased (+86%, P<0.05) and the expression of GLUT-4 was decreased (-28%, P<0.05) in surviving myocardium of infarct-containing hearts. Protein level of GLUT-1 was increased (+81%, P<0.05) and that of GLUT-4 slightly, but not significantly, decreased (-16%, P=NS). mRNA expressions of heart fatty acid binding protein (H-FABP), and of medium chain acyl-CoA dehydrogenase (MCAD), were decreased by 36% (P<0.05) and 35% (P=0. 07), respectively. Eight weeks after acute infarction, the left ventricle was hypertrophied and, at this time-point, there was no difference in the expression of GLUT-1 and GLUT-4 between infarcted and sham-operated hearts. However, myocardial mRNA and protein content of MCAD were decreased by 30% (P<0.01) and 27% (P<0.05), respectively. In summary, in surviving myocardium, glucose oxidation was increased eight weeks after coronary occlusion. Concomitantly, mRNA and protein expression of MCAD were decreased, compatible with a role of altered expression of regulatory proteins of metabolism in post-infarction modification of myocardial metabolism.

Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction.

BACKGROUND: Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. METHODS: The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow-up for 33,389 HIV-infected patients from December 1999 through February 2006. RESULTS: The proportion of patients at high risk of CVD increased from 35.3% during 1999-2000 to 41.3% during 2005-2006. Of 28,985 patients, 2801 (9.7%) initiated lipid-lowering therapy; initiation of lipid-lowering therapy was more common for those with abnormal lipid values and those with traditional risk factors for CVD (male sex, older age, higher body mass index [calculated as the weight in kilograms divided by the square of the height in meters], family and personal history of CVD, and diabetes mellitus). After controlling for these, use of lipid-lowering drugs became relatively less common over time. The incidence of myocardial infarction (0.32 cases per 100 person-years [PY]; 95% confidence interval [CI], 0.29-0.35 cases per 100 PY) appeared to remain stable. However, after controlling for changes in risk factors for CVD, the rate decreased over time (relative rate in 2003 [compared with 1999-2000], 0.73 cases per 100 PY [95% CI, 0.50-1.05 cases per 100 PY]; in 2004, 0.64 cases per 100 PY [95% CI, 0.44-0.94 cases per 100 PY]; in 2005-2006, 0.36 cases per 100 PY [95% CI, 0.24-0.56 cases per 100 PY]). Further adjustment for lipid levels attenuated the relative rates towards unity (relative rate in 2003 [compared with 1999-2000], 1.06 cases per 100 PY [95% CI, 0.63-1.77 cases per 100 PY]; in 2004, 1.02 cases per 100 PY [95% CI, 0.61-1.71 cases per 100 PY]; in 2005-2006, 0.63 cases per 100 PY [95% CI, 0.36-1.09 cases per 100 PY]). CONCLUSIONS: Although the CVD risk profile among patients in the Data Collection on Adverse Events of Anti-HIV Drugs Study has decreased since 1999, rates have remained relatively stable, possibly as a result of a more aggressive approach towards managing the risk of CVD.

Thrombolyse intracoronarienne comme traitement de l'infarctus en constitution [Intracoronary thrombolysis as a treatment for evolving myocardial infarction].

Myocardial infarction is almost always the consequence of a thrombotic obstruction of one or more coronary arteries. We report our experience with the first 24 cases of intracoronary thrombolysis for recanalization of obstructed coronary arteries. 19 cases were successful, 1 case was partially successful and in 4 instances no reopening was observed. The amount of streptokinase used was 206 000 +/- 107 000 units, and reperfusion was achieved after 37 +/- 27.5 minutes. Recanalization of the vessel was accompanied by cessation of precordial pain and partial or complete normalization of the electrocardiogram. In one case bypass surgery was necessary because of reocclusion. Left ventricular function improvement after thrombolysis was dependent on the time-lag between occlusion and recanalization. These observations confirm others' experience that intracoronary thrombolysis appears to have favorable effects in patients with evolving myocardial infarction.

The impact of fasting on the interpretation of triglyceride levels for predicting myocardial infarction risk in HIV-positive individuals: the D:A:D study.

We assessed whether fasting modifies the prognostic value of these measurements for the risk of myocardial infarction (MI). Analyses used mixed effect models and Poisson regression. After confounders were controlled for, fasting triglyceride levels were, on average, 0.122 mmol/L lower than nonfasting levels. Each 2-fold increase in the latest triglyceride level was associated with a 38% increase in MI risk (relative rate, 1.38; 95% confidence interval, 1.26-1.51); fasting status did not modify this association. Our results suggest that it may not be necessary to restrict analyses to fasting measurements when considering MI risk.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.

BACKGROUND: Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients. METHODS: We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals. FINDINGS: Over 157,912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1.90, 95% CI 1.47-2.45 [p=0.0001] with abacavir and 1.49, 1.14-1.95 [p=0.003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1.49, 1.14-1.95 [p=0.004] with didanosine; 1.89, 1.47-2.45 [p=0.0001] with abacavir). INTERPRETATION: There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.

Atypical Kawasaki disease with peripheral gangrene and myocardial infarction: therapeutic implications.

We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to gangrene is a rare but serious complication of KD in infants younger than 7 months of age. Treatment has been targeted at reducing arterial inflammation, arteriospasm and thrombosis. We report the first patient with incomplete KD and peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating and antithrombotic agent appeared successful, restoring hand and foot perfusion without significant long-term sequelae. However, PGE1 could have supported development of myocardial infarction by shunting blood away from ischaemic areas distal to a giant coronary artery aneurysm with beginning thrombosis. CONCLUSION. Atypical KD with peripheral gangrene appears to react favourably to treatment with PGE1, but needs careful monitoring to detect early signs of cardiac ischaemia.

Cardiac repair with allogeneic mesenchymal stem cells after myocardial infarction.

Over the past decade, use of autologous bone marrow-derived mononuclear cells (BMCs) has proven to be safe in phase-I/II studies in patients with myocardial infarction (MI). Taken as a whole, results support a modest yet significant improvement in cardiac function in cell-treated patients. Skeletal myoblasts, adipose-derived stem cells, and bone marrow-derived mesenchymal stem cells (MSCs) have also been tested in clinical studies. MSCs expand rapidly in vitro and have a potential for multilineage differentiation. However, their regenerative capacity decreases with aging, limiting efficacy in old patients. Allogeneic MSCs offer several advantages over autologous BMCs; however, immune rejection of allogeneic cells remains a key issue. As human MSCs do not express the human leukocyte antigen (HLA) class II under normal conditions, and because they modulate T-cell-mediated responses, it has been proposed that allogeneic MSCs may escape immunosurveillance. However, recent data suggest that allogeneic MSCs may switch immune states in vivo to express HLA class II, present alloantigen and induce immune rejection. Allogeneic MSCs, unlike syngeneic ones, were eliminated from rat hearts by 5 weeks, with a loss of functional benefit. Allogeneic MSCs have also been tested in initial clinical studies in cardiology patients. Intravenous allogeneic MSC infusion has proven to be safe in a phase-I trial in patients with acute MI. Endoventricular allogeneic MSC injection has been associated with reduced adverse cardiac events in a phase-II trial in patients with chronic heart failure. The long-term safety and efficacy of allogeneic MSCs for cardiac repair remain to be established. Ongoing phase-II trials are addressing these issues.

HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study.

BACKGROUND: Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals. METHODS: The prospective observational database of the D:A:D collaboration of 11 cohorts of HIV-infected individuals, including 212 clinics in Europe, the United States and Australia was used. Multivariate Poisson regression was used to assess the effect of HCV or HBV infection on the development of myocardial infarction after adjustment for potential confounders, including cardiovascular risk factors, diabetes mellitus and exposure to antiretroviral therapy. RESULTS: Of 33,347 individuals, 517 developed a myocardial infarction over 157,912 person-years, with an event rate of 3.3 events/1,000 person-years (95% confidence interval [CI] 3.0-3.6). Event rates (95% CIs) per 1,000 person-years in those who were HCV-seronegative and HCV-seropositive were 3.3 (3.0-3.7) and 2.7 (2.2-3.3), respectively, and for those who were HBV-seronegative, had inactive infection or had active infection were 3.2 (2.8-3.5), 4.2 (3.1-5.2) and 2.8 (1.8-3.9), respectively. After adjustment, there was no association between HCV seropositivity (rate ratio 0.86 [95% CI 0.62-1.19]), inactive HBV infection (rate ratio 1.07 [95% CI 0.79-1.43]) or active HBV infection (rate ratio 0.78 [95% CI 0.52-1.15]) and the development of myocardial infarction. CONCLUSIONS: We found no association between HBV or HCV coinfection and the development of myocardial infarction among HIV-infected individuals.

Pronostic à long terme des patients ayant bénéficié d'une thrombolyse au stade aigu de l'infarctus du myocarde [Long-term prognosis for patients undergoing thrombolysis during the acute phase of myocardial infarction]

OBJECTIVE: The objective of this study was to analyse the long-term mortality and morbidity of a group of patients undergoing thrombolysis during the acute phase of myocardial infarction and to determine the factors influencing the prognosis. One hundred and seventy five patients (149 mean and 26 women, mean age: 54 years) were included in a randomized study, comparing the efficacy of 2 thrombolytic substances administered during the acute phase of myocardial infarction. A standard questionnaire was sent to the various attending physicians to follow-up of these 175 patients. RESULTS: The hospital mortality was 5% (9 patients) and 14 patients (9%) died after a mean follow-up of 4.3 +/- 2.1 years. The 5-year actuarial survival was 81%. Fourteen patients (8%) were lost to follow-up and 49 patients (32%) underwent surgical or percutaneous revascularization during follow-up. Revascularized patients had a significantly better survival than non-revascularized patients. The mean left ventricular ejection fraction of patients who died was lower (48% versus 71%) than that of survivors. Patients with an ejection fraction < 40% also had a significantly lower survival (p = 0.01). Patency of the vessel after thrombolysis was associated with a slightly better survival; this difference was not significant. The ejection fraction at 6 month was also significantly higher (60 +/- 10% versus 49 +/- 11%) for patients with a patent artery. Three risk factors for death or reinfarction were identified: age > 65 years at the time of infarction, disease in more than one coronary vessel and absence of angina pectoris before infarction. The probability of a coronary accident varied from 2 to 88% according to the number of risk factors present. At the time of follow-up, 60% of patients presented hypercholesterolaemia versus only 7% before infarction 73% of patients received anticoagulant or antiaggregant treatment and 81% of patients were asymptomatic. CONCLUSION: The mortality and the acute and long-term morbidity of myocardial infarction remain high, as only 34% of our patients did not develop any events during follow-up, despite serious medical management and follow-up. The ejection fraction has an important prognostic value. Patient management should take the abovementioned risk factors into account.