Characteristics of Patients With Diabetes Having Normal Coronary Arteries.

We evaluated the association between risk variables in diabetic patients with normal and diseased coronary arteries in a retrospective cohort study conducted at Rashid Hospital, Dubai. A total of 4446 patients underwent coronary angiography due to various indications; 43% had type 2 diabetes mellitus (T2DM). Among the diabetic patients, 94% had diseased coronary arteries and the remaining 6% had absolutely normal arteries. The normal coronary group had significantly lower low-density lipoprotein cholesterol (LDL-C) and a higher high-density lipoprotein cholesterol (HDL-C) levels than the diseased group. Patients with normal coronaries were more likely to be females, have T2DM for a shorter duration, and were nonsmokers and non-South Asians. They also had lower levels of LDL, hemoglobin A1c, and fasting glucose and higher levels of HDL-C. Apart from these variables, genetic or environmental factors could protect these patients from atherosclerosis.

The mystery of recurrent idiopathic cerebrovascular and coronary arterial thrombosis.

A 46-year-old man presented to our hospital with ST elevation myocardial infarction (STEMI). Previous records revealed a history of recurrent non-STEMI, stroke and transient ischaemic attacks. He was thoroughly investigated with coronary angiography, a cerebral CT angiography, thrombophilia panel and autoimmune screening tests, all of which proved negative. His current episode of STEMI resulted while on dual antiplatelet therapy; the patient was investigated for P2Y12 receptor resistance, which was also negative. A diagnosis of idiopathic recurrent arterial thrombosis was established and the patient was discharged home on aspirin and warfarin. Routine follow-up has revealed no recurrence of symptoms.

Blood pressure and other determinants of new-onset atrial fibrillation in patients at high cardiovascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease studies.

BACKGROUND: Evidence on new-onset atrial fibrillation in high-risk vascular patients without heart failure is limited. New-onset atrial fibrillation was a prespecified secondary objective of the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) studies. METHODS: We studied 30 424 ONTARGET/TRANSCEND patients (mean age ±â€ŠSD, 66.4 ±â€Š7.0) with vascular disease or complicated diabetes who were in sinus rhythm at entry. A copy of ECG was sent to central office every time new atrial fibrillation was detected by investigators. RESULTS: During a median follow-up period of 4.7 years, new atrial fibrillation occurred in 2092 patients (15.1 per 1000  patient-years). Risk of atrial fibrillation increased with age, SBP and pulse pressure, left ventricular hypertrophy, BMI, serum creatinine and history of hypertension, coronary artery disease and cerebrovascular disease (all P < 0.01). After adjustment for BMI and other variables, atrial fibrillation risk increased with hip circumference. History of hypertension was associated with a 34% higher risk of new atrial fibrillation. New atrial fibrillation portended an increased risk of congestive heart failure [hazard ratio 2.89, 95% confidence interval (CI) 2.45-3.40, P < 0.01] and cardiovascular death (hazard ratio 1.22, 95% CI 1.05-1.41, P < 0.01). Risk of stroke was unaffected (hazard ratio 1.14, 95% CI 0.93-1.40), whereas that of myocardial infarction was reduced (hazard ratio 0.64, 95% CI 0.50-0.82). Patients with new atrial fibrillation were more likely to receive vitamin K antagonists (P < 0.01), statins (P < 0.05) and ß-blockers (P < 0.01) than those in sinus rhythm. CONCLUSION: New atrial fibrillation is common in high-risk vascular patients and is associated with several risk factors including history of hypertension. Hip circumference was the strongest anthropometric predictor. Despite extensive use of modern therapies, new atrial fibrillation carries a high risk of congestive heart failure and death over a relatively short term.

Vascular rhexis in mice subjected to non-sustained myocardial ischemia and its therapeutic implications.

We previously described the death of vascular cells (vascular rhexis) following persistent coronary occlusion. The present study was designed to determine whether non-sustained ischemia can initiate vascular rhexis and if so, whether relatively brief ischemic insults are sufficient. C57BL6 mice were subjected to coronary ligation for 15 min or 3 h followed by reperfusion. Soluble fractions of left ventricular (LV) homogenates were obtained 48 h after the onset of transitory coronary occlusion. They were assayed by Western blotting for quantification of alpha smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-MHC) that we have shown reflect vascular rhexis delineated immunohistochemically. Non-sustained coronary occlusion for 3 h initiated vascular rhexis evident 45 h after reperfusion, but not earlier, as judged from Western blotting of α-SMA and SM-MHC. The number of small- and medium-sized vessels in the previously ischemic zones was reduced at 45 h after reperfusion as well. Thus, vascular rhexis occurs after ischemia as brief as 3 h but evolves slowly and is not evident for 45 h. The delayed disintegration of the vasculature makes it likely that it can be ameliorated by interventions initiated after non-sustained ischemia, rendering it an attractive target for diminution of phenomena such as late negative LV remodeling, and 'no reflow.'

Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies.

BACKGROUND: cardiovascular risk factors are associated with dementia and cognitive decline. We investigated the effects of renin-angiotensin system blockade on cognitive function in patients aged 55 years and older with established atherosclerotic cardiovascular disease or diabetes with end-organ damage in two clinical trials. METHODS: in the main study, ONTARGET, a double-blind, double-dummy, randomised controlled trial, the effects on cardiovascular outcomes of standard doses of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), an angiotensin-receptor blocker (telmisartan), and a combination of the drugs were evaluated in 25 620 participants. In the parallel TRANSCEND trial, the effects of telmisartan were compared with those of placebo in 5926 participants intolerant to ACE inhibitors. Secondary outcomes included cognitive impairment (defined by investigator-reported diagnosis of dementia or significant cognitive dysfunction, or a score of ≤ 23 on the Mini-Mental State Examination [MMSE]) and cognitive decline (a decrease of ≤ 3 points on the MMSE from baseline during follow-up). Analyses were by intention to treat. We pooled data from these studies to identify baseline predictors of cognitive impairment and its frequency according to mean systolic blood pressure during follow-up. These studies were registered with ClinicalTrials.gov, number NCT00153101. FINDINGS: During a median duration of 56 months (IQR 51-64) of follow-up in ONTARGET, cognitive impairment occurred in 652 (8%) of 7865 patients allocated ramipril, 584 (7%) of 7797 allocated telmisartan, and 618 (8%) of 7807 allocated combination treatment (combination vs ramipril, odds ratio [OR] 0·95, 95% CI 0·85-1·07, p= 0·39; telmisartan vs ramipril, OR 0·90, 0·80-1·01, p = 0·06). Corresponding figures for cognitive decline were 1314 (17%), 1279 (17%), and 1240 (17%) in each of the groups, respectively (telmisartan vs ramipril, OR 0·97, 0·89-1·06, p= 0·53; combination vs ramipril, OR 0·95, 0·88-1·04, p=0·28). In TRANSCEND, cognitive impairment occurred in 239 (9%) of 2694 participants allocated telmisartan compared with 245 (9%) of 2689 allocated placebo (OR 0·97, 0·81-1·17, p= 0·76). The corresponding figures for cognitive decline were 454 (17%) and 412 (16%; OR 1·10, 0·95-1·27, p= 0·22). INTERPRETATION: In patients with cardiovascular disease or diabetes, different approaches to blocking of the renin-angiotensin system had no clear effects on cognitive outcomes. Although patients with the lowest systolic blood pressure had the greatest preservation of cognitive function, meta-regression analyses did not show any benefits of blood-pressure lowering on cognition over several years of treatment.

Meta-analysis of studies of patients in the United Arab Emirates with ST-elevation myocardial infarction treated with thrombolytic agents.

We performed a meta-analysis of 6 studies we conducted in the United Arab Emirates from 1995 to 2009. These included 1,262 patients with ST-elevation myocardial infarction treated with thrombolytic drugs <6 hours after onset of symptoms and signs of myocardial infarction. All patients were treated with tenecteplase or alteplase to induce coronary thrombolysis. Characteristics of patients in all studies were quite similar. Overall mean age was 47 years, 98% were men, 28% had diabetes, 25% were hypertensive, 20% were hyperlipidemic, 56% were smokers, and 9% had sustained previous myocardial infarction. Incidence of adverse outcomes of 30-day mortality (3%), reinfarction (2.5%), stroke (0.4%), or major bleeding (0%) was low compared to global experience with recanalization regardless of how it was induced. There was no incidence of major bleeding requiring transfusion or laparotomy. In conclusion, in predominantly young men in the United Arab Emirates who were admitted and treated early after onset of an acute ST elevation myocardial infarction, recanalization induced by thrombolysis was an attractive therapeutic approach.

Acute coronary syndrome registry from four large centres in United Arab Emirates (UAE-ACS Registry).

OBJECTIVE: To identify the characteristics, treatments and hospital outcomes of patients diagnosed as having acute coronary syndrome (ACS) in the United Arab Emirates (UAE). DESIGN: A 3-year prospective registry. SETTING: Four tertiary care hospitals in three major cities of UAE from December 2003 to December 2006. PATIENTS: 1842 eligible consecutive patients with suspected ACS. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Characteristics, treatments and in-hospital outcomes were recorded. RESULTS: The mean age was 50.8±10.0 years, and 93.1% were male. More than half (51%) had ST elevation myocardial infarction (STEMI). The smoking rate was 46.4%, and diabetes was present in 38.9%. Only a minority (17.3%) used the ambulance services. For patients with STEMI, the median symptom to hospital time was 127 (IQR 60-256) min, and the median diagnostic ECG to thrombolysis time was 28 (IQR 16-50) min. Reperfusion in STEMI was in 81.4% (64.8% thrombolysis and 16.6% primary percutaneous coronary intervention). During hospitalisation, only a minority of the patients did not receive antiplatelets, anticoagulants, beta-blockers, ACE inhibitors and statin therapy. In-hospital complications were not common in our registry cohort. In-hospital mortality was 1.68%. CONCLUSIONS: ACS patients in UAE are young but have higher risk factors such as smoking and diabetes. Almost half present as STEMI. Only a minority use ambulance services.

Erythropoietin to augment myocardial salvage induced by coronary thrombolysis in patients with ST segment elevation acute myocardial infarction.

To determine whether the administration of erythropoietin (EPO) early after the onset of ischemia could enhance the preservation of jeopardized myocardium by reperfusion, 236 patients admitted <6 hours after the onset of chest pain indicative of acute coronary syndromes confirmed to be ST-segment elevation acute myocardial infarctions who were treated with tenecteplase to induce coronary thrombolysis were studied. Patients were randomized to standard care or standard care plus the administration of a single dose of EPO 30,000 IU intravenously immediately before the onset of treatment with tenecteplase. The primary end point was enzymatically estimated infarct size. The results indicated that infarct size index was virtually identical in the 2 groups, with a mean +/- SE of 13.2 +/- 0.1 creatine kinase-MB gram equivalents in controls and 12.4 +/- 0.9 creatine kinase-MB gram equivalents in patients treated with EPO. In conclusion, although the early administration of EPO was apparently safe, it did not enhance the preservation of jeopardized ischemic myocardium.

Very late thrombosis of drug-eluting stents: a brief literature review and case example.

Thrombosis late after implantation is an infrequent but increasingly recognized complication following revascularization with drug-eluting stents (DES). The window of vulnerability for this complication with DES remains undefined. Intermediate-term follow up from pivotal trials and registries suggests continuous separation of event curves out to at least 3 years. We briefly review the evolving body of literature on DES thrombosis and report a case of very late thrombosis 53 months after implantation of a sirolimus-eluting stent. The event occurred despite chronic aspirin monotherapy and represents the longest latency from implantation to thrombosis described in the literature for a DES.

Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia and coronary artery disease (CAD). DESIGN AND SETTING: Prospective, multicentre, randomized, double-blind, placebo-controlled trial conducted in three Middle Eastern countries. PATIENTS: Patients with known CAD, who were being treated with simvastatin 20 mg and had low-density lipoprotein cholesterol (LDL-C) concentrations of 2.6 to 4.1 mmol/l, were randomized to receive daily coadministration of ezetimibe 10 mg or placebo. MAIN OUTCOME MEASURES: The primary outcome was percentage reduction of LDL-C after 6 weeks of randomization. Secondary endpoints included number of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C level and safety and tolerability. RESULTS: We enrolled 144 patients of whom 120 had blood available for final analysis. The coadministration of ezetimibe with ongoing simvastatin therapy resulted in a statistically significant additional reduction in LDL-C concentration as compared with simvastatin monotherapy (-26.7 versus -9.1%, respectively; total additional reduction of 17.6%, P < 0.0001). More patients in the ezetimibe and simvastatin group achieved NCEP ATP III LDL-C target levels than in the simvastatin monotherapy group (70 versus 33%, respectively; P = 0.0001). The coadministration of ezetimibe with simvastatin was well tolerated with a safety profile similar to that of simvastatin monotherapy. CONCLUSION: When coadministered with simvastatin therapy, ezetimibe resulted in significant additional reduction in LDL-C and enabled more patients to achieve NCEP ATP III LDL-C target levels. This was achieved safely and with excellent tolerability.

Heart disease and erythropoietin.

An additional target for reducing infarct size, namely, attenuation of apoptosis, has recently emerged. Erythropoietin (Epo) exhibits properties that may attenuate this process and enhance neovascularization, thereby preserving jeopardized myocardium. Potentially adverse effects of Epo, including hypertension, thrombosis and possible exacerbation of occult neoplasms can likely be averted with analogues such as carbamylated and asialo Epo, which are devoid of erythropoietic effects, yet retain tissue-protective characteristics. With a single, but adequate dose of Epo administered early after the onset of acute myocardial infarction, coupled with therapy to induce reperfusion, tissue protection conferred by Epo and its analogues may facilitate the preservation of myocardium subjected to ischemic insults, thereby improving prognosis.

The potential of erythropoietin for conferring cardioprotection complementing reperfusion.

OBJECTIVES: Despite the well-recognized effects of erythropoietin (EPO) on augmenting red blood cell production, EPO exerts multiple additional effects in diverse tissues. Evidence indicating the potential for tissue protection is reviewed as is a description of a study now initiated, in which its potential benefit on the evolution of acute myocardial infarction in patients is being explored. METHODS: The literature demonstrating tissue-protective effects of EPO in experimental animals and patients is cited as is the protocol of the recently undertaken Vermont/Dubai study assessing the potential benefits conferred by EPO on the evolution of infarction in patients. RESULTS: Compelling arguments can be made indicating that EPO and its congeners, some of which are devoid of erythropoietic effects, can protect tissue against injurious stimuli. Accordingly, the promise of EPO for favorably altering the evolution of acute myocardial infarction merits exploration. Congeners of erythropoietin or EPO itself may be beneficial in protecting the heart against injury induced by ischemia thereby favorably modifying infarct size. Rigorous testing of this hypothesis is now in progress in a study involving patients with acute myocardial infarction admitted to hospital within 6 h after the onset of chest pain in whom infarct size is being evaluated based on serial analyses of concentrations of creatine kinase in plasma and thrombolysis is induced pharmacologically as promptly as possible. CONCLUSION: EPO is promising for myocardial protection. Its potential is being delineated in a clinical study of myocardial infarction treated with tenecteplase with or without concomitant EPO.

Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high risk for cardiovascular disease in clinical practice: A randomized, open-label, parallel-group, multicenter study (DISCOVERY Alpha study).

BACKGROUND: The majority of clinical trials investigating the clinical benefits of lipid-lowering therapies (LLTs) have focused on North American or western and nothern European populations. Therefore, it is timely to confirm the efficacy of these agents in other patient populations in routine clinical practice. OBJECTIVE: The aim of the Direct Statin COmparison of low-density lipoprotein cholesterol (LDL-C) Values: an Evaluation of Rosuvastatin therapY (DISCOVERY) Alpha study was to compare the effects of rosuvastatin 10 mg with those of atorvastatin 10 mg in achieving LDL-C goals in the Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice guidelines. METHODS: This randomized, open-label, parallel-group study was conducted at 93 centers in eastern Europe (Estonia, Latvia, Romania, Russia, Slovenia), Central and South America (Chile, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama), and the Middle East (Israel, Kuwait, Saudi Arabia, United Arab Emirates). Male and female patients aged ≥18 years with primary hypercholesterolemia (LDL-C level, >135 mg/dL if LLT-naive or ≥120 mg/dL if switching statins; triglyceride [TG] level, <400 mg/dL) and a 10-year coronary heart disease (CHD) risk >20% or a history of CHD or other established atherosclerotic disease were eligible for inclusion in the study. Patients were randomly assigned to receive rosuvastatin 10-mg or atorvastatin 10-mg tablets QD for 12 weeks. No formal statistical analyses or comparisons were performed on lipid changes between switched and LLT-naive patients because of the different lipid inclusion criteria for these patients. The primary end point was the proportion of patients achieving 1998 European LDL-C goals after 12 weeks of treatment. A subanalysis was performed to assess the effects of statins in patients who had received previous statin treatment versus those who were LLT-naive. Tolerability was assessed using laboratory analysis and direct questioning of the patients. RESULTS: A total of 1506 patients (52.1% women, 47.9% men; mean [SD] age, 58.2 [10.8] years) participated in the study (rosuvastatin, 1002 patients; atorvastatin, 504 patients; previous LLT, 567 patients). A significantly higher proportion of patients achieved 1998 European LDL-C goals after 12 weeks with rosuvastatin 10 mg than with atorvastatin 10 mg (72.5% vs 56.6%; P < 0.001). Similarly, more patients achieved the 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 10 mg (57.5% vs 39.2%). Rosuvastatin 10 mg was associated with a significantly greater change in LDL-C levels compared with atorvastatin 10 mg, in patients who were LLT-naive (LDL-C: -44.7% vs -33.9%; P < 0.001) and in patients who had received previous LLT (LDL-C: -32.0% vs -26.5%; P = 0.006). TG levels were also decreased with rosuvastatin 10 mg and atorvastatin 10 mg, although there was no significant difference between treatments. Similarly, there was no significant difference in the increase in high-density lipoprotein cholesterol levels between treatments. The most common adverse events overall were headache 16/1497 (1.1%), myalgia 10/1497 (0.7%), and nausea 10/1497 (0.7%). CONCLUSIONS: In this study in patients with primary hypercholesterolemia in clinical practice, greater reductions in LDL-C levels were achieved with a starting dose (10 mg) of rosuvastatin compared with atorvastatin 10 mg, with more patients achieving European LDL-C goals. Both treatments were well tolerated.

Comparison of rapidity of coronary recanalization in men with tenecteplase versus alteplase in acute myocardial infarction.

To determine whether tenecteplase (TNK-t-PA), a bioengineered variant of tissue-type plasminogen activator (t-PA) designed to accelerate thrombolysis, exhibits favorable properties compared with those of alteplase, 266 men were studied

Effect of tenecteplase versus alteplase on platelets during the first 3 hours of treatment for acute myocardial infarction: the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) platelet substudy.

BACKGROUND: Platelets play a pivotal role in the pathogenesis of acute myocardial infarction, as well as in the occurrence of coronary artery reocclusion and bleeding events. Therefore, the success of fibrinolytic therapy may be dependent on its direct effects on platelets. METHODS AND RESULTS: We sought to determine how tenecteplase (TNK) and alteplase (tPA) affect platelets in vitro in human volunteers and ex vivo by use of patient data from the Assessment of the Safety and Efficacy of a New Thrombolytic Agent (ASSENT-2) trial. For the in vitro studies, whole blood from 9 healthy volunteers was incubated with 30 mg TNK and 60 mg tPA. Platelet function was measured by conventional aggregometry, bedside point-of-care devices, and sensitive flow cytometry techniques. For the ex vivo study, 41 patients were selected from the ASSENT-2 trial: 21 had received TNK and 20 had received tPA. Each patient underwent 7 serial blood draws every 30 minutes for 3 hours. Levels of platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, beta-thromboglobulin, platelet factor 4, thromboxane, and prostacyclin were measured by enzyme-linked immunosorbent assay. Significant inhibition of conventional and whole blood aggregation and reduced platelet function by point-of-care analyzers were observed for both agents, but mostly in the TNK-treated samples. After incubation with TNK, flow cytometry revealed decreased expression of glycoprotein IIb/IIIa, PECAM-1, vitronectin receptor, CD151, and formation of the platelet-monocyte aggregates. Serial samples from patients in the ASSENT-2 trial showed a significant decrease of soluble platelet-endothelial biomarkers in the TNK group. There was a trend toward decreased platelet function characteristics with tPA; however, these differences were much smaller than those observed with TNK. CONCLUSIONS: Both tPA and TNK were shown to affect platelet function in human volunteers and in patients with AMI early after thrombolysis. The antiplatelet properties of TNK were shown to be more profound than those of tPA. These findings are relevant to ongoing investigations of combination therapy with fibrinolytic and antiplatelet agents in patients with AMI.