Effects of gender and race on prognosis after myocardial infarction: Adverse prognosis for women, particularly black women

Controversy has arisen concerning whether gender influences the prognosis after myocardial infarction. Although some studies have shown there to be no difference between the sexes, most have indicated a worse prognosis for women, attributing this to differences in baseline characteristics. It has been further suggested that black women have a particularly poor prognosis after infarction. To determine the contribution of gender and race to the course of infarction, 816 patients with confirmed myocardial infarction who were enrolled in the Multi-center Investigation of the Limitation of Infarct Size (MILIS) were analyzed. Of those patients, 226 were women and 590 were men, 142 were black and 674 were white.The cumulative mortality rate at 48 months was 36% for women versus 21% for men (p < 0.001, mean follow-up 32 months). The cumulative mortality rate by race was 34% for blacks versus 24% for whites (p < 0.005). Both women and blacks exhibited more baseline characteristics predictive of mortality than did their male or white counterparts. It was possible to account for the greater mortality rate of blacks by identifiable baseline variables; however, even after adjustment, the mortality rate for women remained significantly higher (p < 0.002). The poorer prognosis for women was influenced by a particularly high mortality rate among black women (48%); the mortality rate for white women was 32%, for black men 23% and for white men 21%. The mortality for black women was significantly greater than that of the other subgroups. Thus, findings in the MILIS population indicate that the prognosis after myocardial infarction is worse for women, particularly black women

Chylous ascites as the main manifestation of left ventricular dysfunction: a case report

BACKGROUND: Ascites is one of the most common complications of liver diseases, even though in 15% of the cases it is related to extrahepatic diseases; 3% are of cardiac nature and they appear associated with signs and symptoms of heart failure. CASE PRESENTATION: A 70 year old man was admitted with more than one year history of abdominal distension and a weight gain of 10 kilograms. He is asymptomatic and walks 2000–3000 meters a day without angor or dyspnea. The physical examination shows moderate abdominal distension, with no hepatosplenomegaly or edema, and there is mild jugular vein distension. The studies performed (complete laboratory work up, paracentesis, liver biopsy, echocardiogram, intrahepatic pressure measurements, etc.) showed a chylous ascites related to portal hypertension, and left ventricular dysfunction was the only probable cause found. CONCLUSION: Asymptomatic heart dysfunction can mimic liver disease and should be kept in mind as a cause of chylous ascites

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

The association between clinical integration of care and transfer of veterans with acute coronary syndromes from primary care VHA hospitals

BACKGROUND: Few studies report on the effect of organizational factors facilitating transfer between primary and tertiary care hospitals either within an integrated health care system or outside it. In this paper, we report on the relationship between degree of clinical integration of cardiology services and transfer rates of acute coronary syndrome (ACS) patients from primary to tertiary hospitals within and outside the Veterans Health Administration (VHA) system. METHODS: Prospective cohort study. Transfer rates were obtained for all patients with ACS diagnoses admitted to 12 primary VHA hospitals between 1998 and 1999. Binary variables measuring clinical integration were constructed for each primary VHA hospital reflecting: presence of on-site VHA cardiologist; referral coordinator at the associated tertiary VHA hospital; and/or referral coordinator at the primary VHA hospital. We assessed the association between the integration variables and overall transfer from primary to tertiary hospitals, using random effects logistic regression, controlling for clustering at two levels and adjusting for patient characteristics. RESULTS: Three of twelve hospitals had a VHA cardiologist on site, six had a referral coordinator at the tertiary VHA hospital, and four had a referral coordinator at the primary hospital. Presence of a VHA staff cardiologist on site and a referral coordinator at the tertiary VHA hospital decreased the likelihood of any transfer (OR 0.45, 95% CI 0.27–0.77, and 0.46, p = 0.002, CI 0.27–0.78). Conversely, having a referral coordinator at the primary VHA hospital increased the likelihood of transfer (OR 6.28, CI 2.92–13.48). CONCLUSIONS: Elements of clinical integration are associated with transfer, an important process in the care of ACS patients. In promoting optimal patient care, clinical integration factors should be considered in addition to patient characteristics

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

&lt;p&gt;Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.&lt;/p&gt; &lt;p&gt;Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (&#60;2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).&lt;/p&gt; &lt;p&gt;Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).&lt;/p&gt

The oxygen consumption paradox of “stunned myocardium” in dogs

The contractile state of the heart is a major determinant of myocardial oxygen consumption. Since regional myocardial contractility can be severely impaired following a transient coronary occlusion, post-ischemic myocardium is frequently assumed to consume less oxygen. To test this assumption, regional myocardial function and oxygen consumption were studied in ancsthetized dogs during 2 h of myocardial reperfusion following either a 15-min (Group I) or 4-h (Group II) left anterior descending coronary artery occlusion. Both groups developed similar post-ischemic regional dysfunction characterized by paradoxical motion (negative shortening). Measured as a percent of baseline segment shortening, anterior wall function in Group I (n=8) and Group II (n=5) at 30 min of reperfusion was −33±11% and −34±16% (p=NS) and at 120 min was −23±9% and −40±16% (p=NS). However, the two groups showed a marked difference in regional myocardial oxygen consumption during reperfusion. Despite the abnormal wall motion, regional oxygen consumption in Group I at 30 and 120 min of reperfusion was unchanged from pre-ischemic levels as measured as a percent of bascline: 104±20% (p=NS) and 111±21% (p=NS). In contrast, regional oxygen consumption in Group II was markedly depressed from bascline at 30 and 120 min of reperfusion: 42±7% (p<.01) and 40±8% (p<.01). To determine whether the dissociation between regional myocardial oxygen consumption and function in Group I was related to mitochondrial uncoupling, six additional dogs were studied. Tissue samples were obtained from post-ischemic myocardium after 120 min of reperfusion following a 15-min coronary artery occlusion, and compared to non-ischemic myocardium. There were no differences in the in vitro mitochondrial respiratory rates or oxidative phosphorylation capacity between the post-ischemic and non-ischemic myocardium. Therefore, in the post-ischemic myocardium, significant depressions in regional contractility may not be associated with falls in oxygen consumption. Following a 15-min coronary artery occlusion, the injured myocardium maintains a paradoxically high oxygen consumption with normal mitochondrial function despite decreased contractility and abnormal wall motion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41748/1/395_2005_Article_BF01906965.pd

c-kitpos GATA-4 High Rat Cardiac Stem Cells Foster Adult Cardiomyocyte Survival through IGF-1 Paracrine Signalling

Resident c-kit positive (c-kitpos) cardiac stem cells (CSCs) could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential.We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs) were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs.c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway

Circulating Apoptotic Progenitor Cells in Patients with Congestive Heart Failure

Background: Circulating CD34+ endothelial progenitor cells (EPCs) are capable of differentiating into mature endothelial cells to assist in angiogenesis and vasculogenesis. We sought to quantify the numbers of apoptotic progenitors in patients with congestive heart failure. Methods and Results: Peripheral blood mononuclear cells were isolated by Ficoll density-gradient from 58 patients with various degrees of heart failure and 23 matched controls. Apoptosis in progenitor CD34+ cells was assessed using the Annexin V-PE/PI detection kit, and FACS analysis was performed with triple staining for CD34, annexin-V and propidium iodide. The percentage of early and late apoptotic progenitor cells was determined in the subject groups and was correlated with clinical characteristics. While there was no significant difference in total CD34 positive cells or early apoptotic progenitors between control subjects and CHF patients (p = 0.42) or between severe and mild/moderate CHF groups (p = 0.544), there was an elevated number of late apoptotic progenitors in the severe CHF group compared with the mild/moderate CHF group (p = 0.03). Late apoptotic progenitors were significantly increased in CHF patients as compared to matched controls. There was also an inverse correlation between late apoptotic progenitors and ejection fraction (r = 20.252, p = 0.028) as well as a positive association with NYHA class (r = 0.223, p = 0.046). Conclusion: Severe heart failure patients exhibited higher numbers of late apoptotic progenitors, and this was positivel

Delphi-Consensus Weights for Ischemic and Bleeding Events to Be Included in a Composite Outcome for RCTs in Thrombosis Prevention

To weight ischemic and bleeding events according to their severity to be used in a composite outcome in RCTs in the field of thrombosis prevention.Using a Delphi consensus method, a panel of anaesthesiology and cardiology experts rated the severity of thrombotic and bleeding clinical events. The ratings were expressed on a 10-point scale. The median and quartiles of the ratings of each item were returned to the experts. Then, the panel members evaluated the events a second time with knowledge of the group responses from the first round. Cronbach's a was used as a measure of homogeneity for the ratings. The final rating for each event corresponded to the median rating obtained at the last Delphi round.Of 70 experts invited, 32 (46%) accepted to participate. Consensus was reached at the second round as indicated by Cronbach's a value (0.99 (95% CI 0.98-1.00)) so the Delphi was stopped. Severity ranged from under-popliteal venous thrombosis (median = 3, Q1 = 2; Q3 = 3) to ischemic stroke or intracerebral hemorrhage with severe disability at 7 days and massive pulmonary embolism (median = 9, Q1 = 9; Q3 = 9). Ratings did not differ according to the medical specialty of experts.These ratings could be used to weight ischemic and bleeding events of various severity comprising a composite outcome in the field of thrombosis prevention