Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Risk of Recurrent Cardiac Events After Onset of Menopause in Women With Congenital Long-QT Syndrome Types 1 and 2
- Birth Weight Predicts Risk of Cardiovascular Disease Within Dizygotic but Not Monozygotic Twin Pairs: A Large Population-Based Co-Twin–Control Study
- Blood Pressure Targets in Subjects With Type 2 Diabetes Mellitus/Impaired Fasting Glucose: Observations From Traditional and Bayesian Random-Effects Meta-Analyses of Randomized Trials
- Sensitive Cardiac Troponin T Assay and the Risk of Incident Cardiovascular Disease in Women With and Without Diabetes Mellitus: The Women's Health Study
- Five-Year Clinical and Angiographic Outcomes of a Randomized Comparison of Sirolimus-Eluting and Paclitaxel-Eluting Stents: Results of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization LATE Trial
- Impact of Leukocyte Count on Mortality and Bleeding in Patients With Myocardial Infarction Undergoing Primary Percutaneous Coronary Interventions: Analysis From the Harmonizing Outcome With Revascularization and Stent in Acute Myocardial Infarction Trial
- Calcineurin Splicing Variant Calcineurin Aβ1 Improves Cardiac Function After Myocardial Infarction Without Inducing Hypertrophy
- Predictors of Abdominal Aortic Aneurysm Sac Enlargement After Endovascular Repair
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Risk of Recurrent Cardiac Events After Onset of Menopause in Women With Congenital Long-QT Syndrome Types 1 and 2
Prior studies have shown that women with congenital long-QT syndrome experience increased risk for cardiac events after the onset of adolescence and during the postpartum period. This risk increase was shown to be more pronounced among women with the LQT2 genotype, suggesting that sex hormones may modify the clinical course of patients with this inherited arrhythmic disorder. The present study is the first to assess the clinical course of long-QT syndrome women after the onset of menopause. We show a genotype-specific association with the risk for cardiac events during the perimenopausal period, including a pronounced increase in the risk for cardiac events (dominated by recurrent episodes of syncope) among LQT2 women and an opposite reduction in the rate of cardiac events in LQT1 women. Notably, the pronounced effect of menopause on the clinical course of long-QT syndrome women was independent of the administration of estrogen therapy. The study also shows that β-blocker therapy is associated with a significant reduction in the risk of recurrent episodes of syncope in long-QT syndrome women during this time period, supporting the continued use of this mode of medical therapy in all women with the LQT2 genotype (without contraindications) even after the onset of menopause. Thus, the present findings suggest that a genotype-specific approach should be used for risk assessment and management of long-QT syndrome women even after the onset of menopause. See p 2784.
Birth Weight Predicts Risk of Cardiovascular Disease Within Dizygotic but Not Monozygotic Twin Pairs: A Large Population-Based Co-Twin–Control Study
Weight at birth has consistently been shown to predict risk of cardiovascular disease (CVD). When considering birth weight as a proxy for the fetal environment, this has prompted theories of early life determinants of adult disease. Although this field of research has come to include exposures that may be independent of birth weight, the underlying mechanisms of the original association remain to be elucidated. Birth weight has many determinants, which, if also involved in CVD development, could explain the association between the two. Since twin siblings share early environment and a varying degree of genetic factors, assessing the association between birth weight and risk of CVD within twin pairs offers unique possibilities to explore the influence from these factors. In this study, we identified 1942 twin pairs discordant for CVD in a population-based cohort of like-sexed twins born in Sweden 1926–1958. Birth weight was found to be inversely associated with risk of CVD within dizygotic, but not monozygotic twin pairs. Similar to previous findings in singletons, associations were seen for both coronary heart disease and ischemic stroke, but only within dizygotic twin pairs. Our study thus lends no support for an association between birth weight and CVD in the absence of genetic differences. We believe these findings make an important contribution to the understanding of early life influence on adult disease, by indicating that the association between birth weight and CVD could be a result of common causes. See p 2792.
Blood Pressure Targets in Subjects With Type 2 Diabetes Mellitus/Impaired Fasting Glucose: Observations From Traditional and Bayesian Random-Effects Meta-Analyses of Randomized Trials
Most guidelines for treatment of hypertension, including the seventh report of the Joint National Committee, recommend an aggressive blood pressure goal of <130/80 mm Hg for patients with diabetes mellitus. However, the evidence on which the guidelines are based is limited. In our analyses of 13 randomized trials with 37 736 participants, we noted that in patients with type 2 diabetes mellitus, a systolic blood pressure treatment goal of 130 to 135 mm Hg is acceptable. However, with more aggressive goals (<130 mm Hg), we observed target organ heterogeneity in that the risk of stroke continued to fall, but there was no benefit regarding the risk of other macrovascular or microvascular (cardiac, renal, and retinal) events, and the risk of serious adverse events even increased. See p 2799.
Sensitive Cardiac Troponin T Assay and the Risk of Incident Cardiovascular Disease in Women With and Without Diabetes Mellitus: The Women's Health Study
Cardiac troponin is the preferred marker of myocardial necrosis in patients with acute coronary syndromes, and a strong predictor of adverse outcome in patients with chronic heart failure or coronary heart disease. However, troponin is rarely detectable in healthy patients when conventional assays are used. Whether very low levels of troponin detected by a novel high-sensitivity assay are associated with adverse outcomes in otherwise healthy diabetic and nondiabetic women has not been well studied. Using a new, highly sensitive assay for cardiac troponin T, we found that a higher proportion of diabetic women (45.5%) than nondiabetic women (30.3%) had detectable levels of cardiac troponin. Among diabetic women, the presence of a detectable troponin was associated with a 79% increase in the risk of incident cardiovascular disease (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) after adjusting for traditional cardiovascular risk factors and hemoglobin A1c. This increased risk in diabetic women appeared to be driven by a 3-fold increase in the risk of cardiovascular death. By contrast, no increase in cardiovascular risk was observed among women without diabetes mellitus. These data raise the possibility that high sensitivity troponin could serve as a complimentary marker of cardiovascular risk and a means of further risk stratification in women with diabetes mellitus. See p 2811.
Five-Year Clinical and Angiographic Outcomes of a Randomized Comparison of Sirolimus-Eluting and Paclitaxel-Eluting Stents: Results of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization LATE Trial
First-generation drug-eluting stents releasing sirolimus or paclitaxel from durable polymers have reduced restenosis compared with bare metal stents in a broad spectrum of patients and lesion subsets. Sirolimus-eluting stents (SES) have been shown to be more effective than paclitaxel-eluting stents (PES) in most studies with angiographic follow-up up to 1 year. However, the differential safety profile of SES and PES during long-term follow-up has not been established. Moreover, the phenomenon of very late stent thrombosis emerged among more complex patients, and long-term data from randomized trials with the unrestricted use of drug-eluting stents are not available. A total of 1012 patients were randomly assigned to SES or PES and followed for up to 5 years as part of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) LATE trial. Initial advantages of SES over PES in major adverse cardiac events and target lesion revascularization were partially canceled out by subsequent advantages of PES over SES (P for interaction <0.001). Major adverse cardiac events occurred in 19.7% of SES- and 21.4% of PES-treated patients (P=0.39) at 5 years. Similarly, there were no differences in terms of cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis. Repeat angiography was completed in 43.8% at 5 years. The delayed lumen loss amounted to 0.37±0.73 mm among SES-treated patients and 0.29±59 mm among PES-treated patients (P=0.32). The increase in late loss and the ongoing risk of very late stent thrombosis (annual rate of 0.65%) suggest incomplete vascular healing up to 5 years in patients with first-generation drug-eluting stents. See p 2819.
Impact of Leukocyte Count on Mortality and Bleeding in Patients With Myocardial Infarction Undergoing Primary Percutaneous Coronary Interventions: Analysis From the Harmonizing Outcome With Revascularization and Stent in Acute Myocardial Infarction Trial
The relationship between the baseline white blood cell count and mortality in patients with ST-segment–elevation acute myocardial infarction treated with percutaneous coronary intervention is poorly understood. Furthermore, whether there is a relationship between white blood cell count and the risk of noncardiac mortality, bleeding, and infarct size after percutaneous coronary intervention is unknown. From the large-scale Harmonizing Outcome With Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial, we have demonstrated that (1) the baseline white blood cell count drawn at the time of presentation with ST-segment–elevation acute myocardial infarction was an independent predictor of the 1-year rates of all-cause mortality, cardiac mortality, noncardiac mortality, and major bleeding after primary percutaneous coronary intervention and (2) elevated white blood cell count at baseline was also an independent determinant of peak creatinine phosphokinase (a direct indicator of infarct size) after primary percutaneous coronary intervention for ST-segment–elevation acute myocardial infarction. Therefore, the baseline white blood cell count, which is routinely obtained at the time of admission in patients with ST-segment–elevation acute myocardial infarction, is an important prognostic predictor of infarct size, major bleeding, and cardiac and noncardiac mortality after primary percutaneous coronary intervention. Further studies are required to determine whether these associations are causal. See p 2829.
Calcineurin Splicing Variant Calcineurin Aβ1 Improves Cardiac Function After Myocardial Infarction Without Inducing Hypertrophy
Because the adult mammalian heart has limited regenerative capacity, the considerable loss of cardiomyocytes after myocardial infarction leads to the formation of a permanent scar and the onset of numerous pathological events that culminate in heart failure. Modulating this response may lessen the consequences of myocardial infarction and offers opportunity for therapeutic intervention. In this work, we explored the potential benefit of cardiac overexpression of calcineurin Aβ1 (CnAβ1), an alternative splicing isoform of the phosphatase calcineurin found in both progenitor cells and regenerative tissues. Although other calcineurin isoforms play a detrimental role in heart disease, a unique domain in the carboxy-terminus of the protein confers CnAβ1 the ability to activate a protective pathway in the cardiomyocyte. Mice overexpressing CnAβ1 show significantly improved cardiac function and reduced scar formation after infarction. We identified the underlying molecular mechanism to be interaction between CnAβ1 and mTOR complex 2 and subsequent activation of the Akt pathway and amino acid biosynthesis response. This work suggests that alternative splicing isoforms of the same protein can have opposite effects on heart pathophysiology and highlights manipulation of alternative splicing in general, and induction of CnAβ1 in particular, as a future therapeutic approach. See p 2838.
Predictors of Abdominal Aortic Aneurysm Sac Enlargement After Endovascular Repair
Two recently published randomized trials comparing the effectiveness of open surgical and endovascular repair (EVAR) for the treatment of abdominal aortic aneurysms have demonstrated a significantly lower mortality rate for patients undergoing EVAR. However, the initial short-term survival advantage for patients undergoing EVAR was lost after long-term follow-up. A significant proportion of the late deaths of patients undergoing EVAR were due to aneurysm rupture. These concerning findings raise questions about the effectiveness and durability of EVAR to prevent death caused by abdominal aortic aneurysm rupture. This study uses a large multicenter cohort of patients who underwent endovascular abdominal aortic aneurysm repair in the United States. This data set is the largest EVAR cohort assembled to date that contains standardized, validated computed tomography anatomic measurements performed on all patients before and after EVAR. We demonstrate that compliance with published EVAR device guidelines is low, and that the incidence of aneurysm sac enlargement after EVAR is high. These unexpected findings raise significant concerns about the long-term risk of aneurysm rupture in patients undergoing EVAR in the United States. Furthermore, over the decade of study, liberalization of the anatomic characteristics deemed suitable for EVAR by device manufacturers has occurred, and several of these liberalized anatomic characteristics independently predict aortic aneurysm sac enlargement. See p 2848.
- © 2011 American Heart Association, Inc.
- Predictors of Abdominal Aortic Aneurysm Sac Enlargement After Endovascular Repair
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