G. New

Long-term estrogen therapy improves vascular function in male to female transsexuals.

OBJECTIVES This study sought to examine the effects of long-term estrogen therapy on vascular function in male to female transsexuals and to compare the findings with those observed in men and premenopausal women. BACKGROUND Gender differences in coronary artery disease have largely been attributed to the beneficial effects of estrogen on vascular function and plasma lipids in women. However, the effects of estrogen on the male vasculature have not been widely studied. METHODS We compared the effects of estrogen on vascular function in 14 male to female transsexuals, 14 age-matched men and 15 premenopausal women. Flow-mediated vasodilation and response to nitroglycerin were assessed in the brachial artery using noninvasive ultrasound. RESULTS Flow-mediated vasodilation was similar in transsexuals and women but greater than that in men ([mean +/- SE] 11.5 +/- 1.3% and 9.4 +/- 1.1% vs. 5.2 +/- 1.0% respectively, p < 0.005). Responses to nitroglycerin were also greater in transsexuals and women than in men (21.6 +/- 1.7% and 21.0 +/- 0.9% vs. 14.5 +/- 1.2%, respectively, p = 0.0005). These differences persisted even after adjusting for vessel size. Despite similar total cholesterol levels, transsexuals had high density lipoprotein cholesterol levels similar to those in women and greater than those observed in men (1.76 +/- 0.12 and 1.82 +/- 0.11 mmol/liter vs. 1.35 +/- 0.07 mmol/liter, respectively, p < 0.005). Moreover, triglyceride levels were greater in transsexuals than in men and women, and low density lipoprotein cholesterol (LDL-C) particle size was smaller (25.7 +/- 0.2 nm vs. 26.2 +/- 0.1 and 26.6 +/- 0.1 nm, respectively, p = 0.0001). Serum testosterone (an index of estrogen therapy in transsexuals) was markedly suppressed in transsexuals and similar to that in women. Univariate analysis revealed that there was a strong inverse correlation between serum testosterone and flow-mediated vasodilation (r(s) = -0.48, p < 0.005). Multivariate analysis revealed that the best combination of predictors of flow-mediated vasodilation was serum testosterone, vessel size and LDL-C (R2 = 0.3, p < 0.005). CONCLUSIONS Long-term estrogen therapy appears to improve vascular function in male to female transsexuals and occurs despite higher triglyceride levels and the presence of small, dense LDL-C. The beneficial effects of estrogen are not gender specific or solely mediated through endothelium-derived nitric oxide.

Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans.

Continuous release of nitric oxide contributes to the maintenance of resting tone in the human forearm and coronary circulations; however, evidence for a similar role of vasodilator prostanoids such as prostacyclin is lacking. We examined whether continuous release of prostacyclin contributes to basal forearm blood flow. Flow was measured using venous occlusion plethysmography in 38 healthy volunteers [mean age 21.3 ± 2.5 yr (±SD); 13 female, 25 male] at rest, after administration of three incremental intra-arterial infusions of either the cyclooxygenase inhibitor aspirin or placebo, and before and after administration of the endothelium-dependent and -independent dilators acetylcholine (30 μg/min) and nitroprusside (1 μg/min). To assess the effect of aspirin on the production of prostacyclin, plasma 6-keto prostaglandin F1α(6-keto-PGF1α; the stable metabolite of prostacyclin) was measured by simultaneous arterial and venous sampling. Aspirin produced a time- and dose-dependent reduction in forearm blood flow, resulting in a 32% decrease at the highest dose. The effect was maximal after 10 min. Flow at rest and after aspirin doses of 1, 3, and 10 mg/min was 2.6 ± 0.2, 2.3 ± 0.2, 2.1 ± 0.2, and 1.8 ± 0.2 ml ⋅ 100 ml forearm tissue-1 ⋅ min-1, respectively (means ± SE, P< 0.001). Commensurate with these data, the net forearm production of 6-keto-PGF1α was 52.9 ± 16.4, 11.7 ± 8.6, 18.7 ± 8.5, and 12.0 ± 12.5 pg ⋅ 100 ml forearm tissue-1 ⋅ min-1 for the respective doses ( P = 0.04). No time-dependent reduction in flow was seen in subjects with vehicle infusion. Aspirin did not affect the responses to acetylcholine or nitroprusside. These data suggest that continuous release of prostacyclin plays a role in the maintenance of resting forearm blood flow. There appears to be a direct link between the reduction in flow with aspirin and inhibition of prostacyclin production.

Survival of Elderly Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction Complicated by Cardiogenic Shock

OBJECTIVES We sought to assess clinical outcomes of elderly patients (age >or=75 years) undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated by cardiogenic shock (CS) in a contemporary multicenter PCI registry. BACKGROUND Although benefits of early PCI have been shown in younger groups, few studies have reported on clinical outcomes in elderly shock patients using current PCI techniques. METHODS We analyzed baseline characteristics and procedural and clinical outcomes in 143 consecutive patients presenting with MI and CS who underwent PCI from the Melbourne Interventional Group registry between 2004 and 2007. RESULTS Of the 143 patients, 31.5% (n = 45) were elderly and 68.5% were younger (age <75 years). Elderly patients were more likely to be female (46.7% vs. 22.4%, p < 0.01) and have hypertension (77.8% vs. 46.4%, p < 0.01), previous MI (31.1% vs. 15.5%, p = 0.03), renal failure (24.4% vs. 11.3%, p < 0.05) and multivessel coronary artery disease (93.1% vs. 68.3%, p < 0.01). Stent (86.7% vs. 94.8%, p = 0.09), glycoprotein IIb/IIIa inhibitor (68.9% vs. 65.3%, p = 0.67), and intra-aortic balloon pump (57.8% vs. 58.2%, p = 0.97) use were similar in both groups. In-hospital, 30-day, and 1-year mortality in the elderly group versus the younger group were 42.2% vs. 33.7% (p = 0.32), 43.2% vs. 36.1% (p = 0.42), and 52.6% vs. 46.8% (p = 0.56), respectively. CONCLUSIONS In this study, the 1-year survival of elderly patients with acute MI complicated by CS undergoing PCI was comparable to younger patients. These data suggest that in elderly patients presenting with CS, benefit is possible with selective use of early revascularization and merits further investigation.

An evaluation of octogenarians undergoing percutaneous coronary intervention from the Melbourne Interventional Group registry

The objective of this study was to evaluate the clinical characteristics and outcomes of octogenarians (≥80 years of age) in a contemporary, multi‐centre percutaneous coronary intervention (PCI) registry.

Usefulness of Transient and Persistent No Reflow to Predict Adverse Clinical Outcomes Following Percutaneous Coronary Intervention

The no reflow phenomenon is reported to occur in >2% of all percutaneous coronary interventions (PCIs) and portends a poor prognosis. We analyzed data from 5,286 consecutive patients who underwent PCI from the Melbourne Interventional Group (MIG) registry from April 2004 through January 2008 who had 30-day follow-up completed. Patients without no reflow (normal reflow, n = 5,031) were compared to 255 (4.8%) with no reflow (n = 217 for transient no reflow, n = 38 for persistent no reflow). Patients with transient or persistent no reflow were more likely to present with ST-elevation myocardial infarction (MI) or cardiogenic shock (p <0.0001 for the 2 comparisons). They were also more likely to have complex lesions (American College of Cardiology/American Heart Association type B2/C), have lesions within a bypass graft, require an intra-aortic balloon pump, receive glycoprotein IIb/IIIa inhibition, and have a longer mean stent length (p <0.0001 for all comparisons). In-hospital outcomes were significantly worse in those patients with transient or persistent no reflow, with increased death, periprocedural MI, renal impairment, and major adverse cardiac events (p <0.0001 for all comparisons). Similarly, transient and persistent no reflow portended worse 30-day clinical outcomes, with a progressive increase in mortality (normal reflow 1.7% vs transient no reflow 5.5% vs persistent no reflow 13.2%, p <0.0001), MI, target vessel revascularization, and major adverse cardiac events (p <0.0001 for all comparisons) compared to patients with normal flow. In conclusion, transient or persistent no reflow complicates approximately 1 in 20 PCIs and results in stepwise increases in in-hospital and 30-day adverse outcomes.

Five-minute heart rate variability can predict obstructive angiographic coronary disease

Objective Obstructive coronary artery disease (CAD) is evident in only half of patients referred for diagnostic angiography. Five-minute heart rate variability (HRV) is a non-invasive marker for autonomic control of the vasculature, which this study hypothesised could risk-stratify cardiac patients and reduce unnecessary angiograms. Design A prospective observational study (the Alternative Risk Markers in Coronary Artery Disease (ARM–CAD) study). Setting Three cardiac centres in Melbourne, Australia. Patients 470 consecutive patients undergoing elective angiography (with predominantly normal cardiac rhythm), regardless of co-morbidity. Main outcome measures The presence of obstructive CAD (≥50% stenosis) on angiography. Results Patients with obstructive CAD had significantly reduced HRV, particularly in the low frequency (LF) range (median 180 vs 267 ms2 without CAD; p<0.001). There was a linear trend with the severity of CAD; median LF power (IQR) in patients with normal coronaries was 275 (612), with minor coronary irregularities 255 (400), single-vessel CAD 212 (396) and more severe disease 170 (327) ms2; p value for trend 0.003. There was a similar reduction in LF power regardless of the anatomical location of coronary stenoses. Comparing patients with LF less than 250 and 250 ms2 or greater, the adjusted OR for obstructive CAD using multivariate regression was 2.42, 95% CI 1.33 to 4.38 (p=0.004). No interactions were noted in subgroup analysis and HRV added to risk prediction irrespective of the baseline Framingham risk (p<0.0001). Conclusion Low HRV is strongly predictive of angiographic coronary disease regardless of other co-morbidities and is clinically useful as a risk predictor in patients with sinus rhythm. Clinical trial registration information http://clinicaltrials.gov/ct2/show/NCT00403351 www.armcad.com

Renal impairment is an independent predictor of adverse events post coronary intervention in patients with and without drug-eluting stents.

Renal impairment (RI) is known to be an independent risk factor for the progression of cardiovascular disease. Its impact, however, on the outcomes in patients undergoing percutaneous coronary intervention (PCI) especially in the era of drug-eluting stents (DES) is not well known. We analysed data from patients undergoing PCI from April 1, 2004, to September 30, 2006, who were part of the Melbourne Interventional Group registry. RI was defined as an estimated glomerular filtration rate (eGFR), calculated using Cockcroft-Gault formula, of <60 ml/min. We compared outcomes at 30 days and 12 months in patients with and without RI. Four thousand one hundred ninety-five patients (3043 male) with an average age 65+/-12 years (mean+/-S.D.) underwent PCI. Twelve-month follow-up was available in 3963 (95%) patients, and these were included in the analysis. One thousand twelve patients (26%) had RI; of these, 608 (60%) presented with an acute coronary syndrome. Both 30-day major adverse cardiac events (MACE), 9.1% vs. 4.6% (P<.01), and all-cause mortality, 4.5% vs. 0.7% (P<.01), were significantly higher in those with RI compared to those without RI. Twelve-month mortality (8.8% vs. 1.7%, P<.01) and MACE (19.7% vs. 10.3%, P<.01) were also significantly higher in those with RI. In multiple regression analysis, RI was an independent predictor of 12-month MACE [OR 2.0 (CI 1.6-2.6), P<.01]. RI is an independent predictor of 30-day and 12-month MACE and death after PCI in patients with stable and unstable coronary syndromes, even with widespread use of DES. eGFR should be used to help risk-stratify patients undergoing PCI.

Long-term oestrogen therapy is associated with improved endothelium-dependent vasodilation in the forearm resistance circulation of biological males.

1. The aim of the present study was to determine the effects of long‐term oestrogen on resistance vessel reactivity in biological males.

The effect of intended duration of clopidogrel use on early and late mortality and major adverse cardiac events in patients with drug-eluting stents.

BACKGROUND The optimal duration of clopidogrel use for prevention of stent thrombosis with drug-eluting stent (DES) use is uncertain. Our objective was to determine whether the planned duration of clopidogrel at the time of percutaneous coronary intervention affected patient outcomes. METHODS We analyzed data from 2,980 patients who underwent percutaneous coronary intervention in the Melbourne Interventional Group registry who had 12-month follow-up. We compared outcomes at 30 days and 12 months according to planned duration of clopidogrel use. RESULTS Twelve-month mortality was significantly lower in patients with a DES with a longer (>or=12 months) planned duration of clopidogrel when compared with a shorter (<or=6 months) planned duration (2.8% vs 5.3%, P = .012). However, myocardial infarction, target-vessel revascularization, and overall major adverse cardiac events were similar in the longer- and shorter-duration clopidogrel strategies. In contrast, in patients receiving a bare-metal stent, mortality at 12 months was similar among the clopidogrel-duration strategies. Kaplan-Meier analysis demonstrated improved cumulative survival with planned clopidogrel use of >or=12 months (log rank P = .017), and the propensity score-adjusted odds ratio was 0.59 (95% confidence interval 0.35-0.99, P = .04). Premature cessation of clopidogrel in DES patients was documented in 5.2% of patients alive at 30-day follow-up, and these patients had increased 12-month mortality (10.6% vs 1.4%, P < .0001) and major adverse cardiac events (22.4% vs 12.0%, P = .005). CONCLUSIONS These data suggest that in patients treated with DES, longer (>or=12 months) planned duration of clopidogrel results in reduced 12-month mortality and that premature cessation of clopidogrel results in significantly higher event rates. Randomized studies are urgently needed to address this issue.

Impact of Periprocedural Atrial Fibrillation on Short-Term Clinical Outcomes Following Percutaneous Coronary Intervention

There are few data on the incidence and clinical outcomes of patients with atrial fibrillation (AF) treated in the era of percutaneous coronary intervention (PCI). We analyzed 30-day clinical outcomes in 3,307 consecutive patients with and without AF (sinus rhythm) undergoing PCI from January 2007 through December 2008 enrolled in a multicenter Australian registry. Periprocedural AF was present in 162 patients (4.9%). AF was associated with older age (74.1 ± 8.9 vs 63.9 ± 11.9 years, p <0.001), higher baseline serum creatinine (0.13 ± 0.14 vs 0.10 ± 0.13 mmol/L, p = 0.01), and lower left ventricular ejection fraction (49.5 ± 13.2% vs 53.4% ± 11.6%, p <0.001). Significantly more patients with AF had a history of heart failure and cerebrovascular and peripheral arterial diseases (p ≤0.01 for all comparisons). Periprocedural glycoprotein IIb/IIIa inhibitor (31.5% vs 31.4%, p = 0.98) and antithrombin use were not different between groups, but in-hospital bleeding complications were higher in patients with AF (5.0% vs 2.1%, p = 0.015). Fewer patients with AF received drug-eluting stents (p = 0.004). AF was associated with a greater than fourfold increase in 30-day mortality (9.9% vs 2.2%, p <0.0001) and readmission rates at 30 days (p = 0.01). Fewer patients with AF were on dual antiplatelet therapy at 30 days (86.3% vs 94.3%, p <0.0001), although 28.1% of patients with AF were on triple therapy (dual antiplatelet therapy plus oral anticoagulation). In conclusion, patients with periprocedural AF represent a very high-risk group. Excess 30-day morbidity and mortality after PCI may be due to the higher incidence of co-morbidities, bleeding complications, and suboptimal antiplatelet therapy.