Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Increased Prevalence of Congenital Heart Defects in Monozygotic and Dizygotic Twins
- High-Density Lipoprotein Cholesterol, Size, Particle Number, and Residual Vascular Risk After Potent Statin Therapy
- Secular Trends in Cardiovascular Disease and Its Risk Factors in Japanese: Half-Century Data From the Hisayama Study (1961-2009)
- Association of Early Physician Follow-Up and 30-Day Readmission After Non–ST-Segment–Elevation Myocardial Infarction Among Older Patients
- Heterogeneity in Lung 18FDG Uptake in Pulmonary Arterial Hypertension: Potential of Dynamic 18FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments
- Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance: Implications for Early Cardiac Remodeling
- Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding: A Randomized, Plasma-Controlled, Phase IIIb Study
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Increased Prevalence of Congenital Heart Defects in Monozygotic and Dizygotic Twins
Half of all twins are born prematurely, and therefore twins more often than singletons experience cardiopulmonary problems such as respiratory distress syndrome and patent ductus arteriosus. In addition, previous smaller studies indicate that congenital heart defects generally may be more common in monochorionic twins (who are all monozygotic) than in dichorionic twins and singletons. We investigated congenital heart defect occurrence in all twins and 5% of all singletons born in Denmark in 1977–2001. Among 41 525 twin individuals, 1.4% had congenital heart defects, whereas the corresponding number for singletons was 0.87%. Patent ductus arteriosus and coarctation of the aorta occurred >3 times as often in twins as in singletons. The increased occurrence in twins was also found in sensitivity analyses including only inpatients or only surgically treated cases regardless of whether preterm patent ductus arteriosus was included. We were not able to demonstrate a higher risk for congenital heart defects among monozygotic twins compared with dizygotic twins, and the congenital heart defect occurrence was also increased in dizygotic twins, who were all dichorionic. Our study shows that congenital heart defect is more common in twins than in singletons, and the increased occurrence is not restricted to monochorionic twins. Intrauterine surveillance and a postnatal comprehensive cardiac assessment for both twins may be considered regardless of chorionicity and zygosity. See p 1182.
High-Density Lipoprotein Cholesterol, Size, Particle Number, and Residual Vascular Risk After Potent Statin Therapy
Chemically measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL measures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy. In JUPITER, HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10 886 participants without cardiovascular disease or diabetes mellitus before and after random allocation to rosuvastatin 20 mg/d or placebo. Median follow-up was 2 years. At baseline, HDL-P correlated moderately with HDL-C (r=0.55) but more strongly with apoA-I (0.69). HDL size showed greater correlation with HDL-C (r=0.65) than with apoA-I (r=0.56), and much less with HDL-P (r=0.22). Among placebo-allocated individuals, on-treatment HDL-C, apoA-I, and HDL-P had similar inverse associations with cardiovascular disease, whereas HDL size was not associated with cardiovascular disease. Among rosuvastatin-allocated individuals in JUPITER, on-treatment HDL-P had a statistically significant and somewhat stronger association with residual vascular risk (adjusted hazard ratio, 0.72; 95% confidence interval, 0.57–0.93; P=0.01) than HDL-C (0.82; 95% confidence interval, 0.63–1.08; P=0.16) or apoA-I (0.86; 95% confidence interval, 0.67–1.10; P=0.22). HDL size was not associated with residual vascular risk or with risk in the absence of statin therapy. This study suggests that HDL-P may be a better clinical marker of residual risk than HDL-C or apoA-I among individuals treated to very low low-density lipoprotein cholesterol levels with potent statin therapy. This has potential implications for evaluating therapeutic interventions targeting HDL in the era of potent low-density lipoprotein cholesterol lowering with statin therapy. See p 1189.
Secular Trends in Cardiovascular Disease and Its Risk Factors in Japanese: Half-Century Data From the Hisayama Study (1961-2009)
The Japanese population has been characterized by a higher incidence and mortality of stroke and a lower incidence and mortality of coronary heart disease than Western populations; however, the recent westernization of lifestyle and advances in medical technology are likely to have affected the incidence and mortality of these diseases in Japan. Using data from 5 cohorts established in different decades over the past half century by the Hisayama Study, a prospective cohort study of cardiovascular disease in Japan, we showed that the incidence and mortality of stroke decreased greatly from the 1960s to the 1970s, but this decreasing trend slowed down recently. In contrast, the incidence of acute myocardial infarction did not show a clear secular change. These trends were likely to be associated with secular changes in cardiovascular risk factors. Although the improvement in hypertension management and the decrease in smoking rate contributed to a decline in stroke incidence, most hypertensive subjects did not achieve a guideline-recommended target blood pressure level of 140/90 mm Hg even in the recent examination in 2002, and smoking rates in men were still much higher than in Western populations. In addition, the increasing rates of metabolic risk factors, such as diabetes mellitus, dyslipidemia, and obesity, are currently the greatest concern, because they may increase the incidence of cardiovascular disease in the near future. Our study suggests that strict blood pressure control, smoking cessation, and intensive management of metabolic risk factors are needed for further prevention of cardiovascular disease in Japan. See p 1198.
Association of Early Physician Follow-Up and 30-Day Readmission After Non–ST-Segment–Elevation Myocardial Infarction Among Older Patients
In the United States, 30-day readmission rates after acute myocardial infarction are common and are now used as a national hospital performance measure. To date, there are limited proven means of reducing readmissions after acute myocardial infarction, although early outpatient physician follow-up after hospitalization for heart failure has been associated with reduced 30-day readmissions. We studied >25 000 older non–ST-segment myocardial infarction patients in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines (CRUSADE) Registry. We found that only a minority (23.3%) of acute myocardial infarction patients received early follow-up within 7 days of discharge and that this rate varied widely among hospitals. However, we found no evidence that hospitals that more commonly used early physician follow-up had lower rates of 30-day all-cause readmission. These null findings were similar among high-risk subgroups and for early cardiology follow-up. Although care transitions from hospital to outpatient care after an acute event may still be important, our data do not suggest that generalized use of early physician follow-up will reduce 30-day readmissions among older adults after acute myocardial infarction. Further studies are needed to investigate other approaches to reduce acute myocardial infarction readmissions. See p 1206.
Heterogeneity in Lung 18FDG Uptake in Pulmonary Arterial Hypertension: Potential of Dynamic 18FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments
Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. This study explores the application of molecular imaging with the use of positron emission tomography as a tool to understand the vascular pathology of PAH and as a bridging biomarker to address the challenge of assessing therapies directed at structural remodeling in PAH. It examines and utilizes the “Warburg” concept that proliferating cells require more glucose. With application of dynamic fluorine-18–labeled 2-fluoro-2-deoxyglucose (18FDG) positron emission tomography data acquisition and kinetic modeling, our data reveal interindividual and intraindividual variability in 18FDG uptake in the lungs of patients with idiopathic PAH. Using an animal model and vascular endothelial cells from idiopathic PAH lungs, we report that the new treatments under development for PAH inhibit glucose metabolism as well as proliferation. We suggest that 18FDG positron emission tomography may offer a tool for deep phenotyping and stratifying idiopathic PAH patients to better understand the response to new PAH-targeted treatments in a clinical trial. See p 1214.
Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance: Implications for Early Cardiac Remodeling
Cardiac hypertrophy is a conserved response to myocardial stress and injury that predates the development of systolic and diastolic dysfunction. Large epidemiological studies have demonstrated the adverse prognostic impact of pathological hypertrophy on the development of stroke, heart failure, and all-cause mortality in at-risk patients with hypertension. In animal models of pressure-overload hypertrophy, there appears to be a progression through cellular hypertrophy, fibrosis, and whole-organ hypertrophy/dysfunction that marks the transition to heart failure, with cellular hypertrophy as one of the earliest myocardial responses. Although in vitro research in these animal models has elucidated pathways of cellular hypertrophy development, the ability to translate these findings in vivo in a serial fashion (to observe the coordinated development of hypertrophy, fibrosis, and dysfunction) has been limited by the availability of noninvasive metrics of cellular hypertrophy and fibrosis. In this report, we present a magnetic resonance–based technique to quantify cardiomyocyte size and interstitial fibrosis noninvasively in 2 models of pressure-overload hypertrophy in mice. This technique, based on a T1-based magnetic resonance imaging determination of the intracellular lifetime of a water molecule, provides a surrogate measure of average cardiomyocyte size and myocardial fibrosis in serial noninvasive examinations, demonstrating the sequential development of hypertrophy and fibrosis in pressure overload. Ultimately, this technique may allow the detection of early hypertrophy phenotypes in human disease for targeting more aggressive prevention and identifying individuals at high risk for progression to heart failure. See p 1225.
Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding: A Randomized, Plasma-Controlled, Phase IIIb Study
The administration of vitamin K antagonists (VKAs) for the management of thromboembolic events is associated with hemorrhagic risk. Patients presenting with acute bleeding require rapid VKA reversal, which can be achieved by administration of either plasma or prothrombin complex concentrate (containing vitamin K–dependent factors). Despite widespread use in the United States, the efficacy of plasma has not been established and is associated with safety concerns such as fluid overload. We report the findings of the first prospective, controlled, randomized, multicenter clinical trial comparing a 4-factor prothrombin complex concentrate with plasma for the urgent reversal of VKAs in patients with acute major bleeding. The study demonstrated that compared with plasma, 4-factor prothrombin complex concentrate was noninferior for the primary end point of hemostatic efficacy at 24 hours, was superior for the coprimary end point of rapid international normalized ratio reduction, and had a similar safety profile. Thus, 4-factor prothrombin complex concentrate can be considered an efficacious alternative to plasma for VKA reversal in patients presenting with major bleeding in time- and volume-critical situations. We believe that this report will be of significant interest to clinicians involved in the management of VKA-related bleeding complications because VKA remains an important anticoagulant therapy for numerous clinical conditions. See p 1234.
- © 2013 American Heart Association, Inc.
- Increased Prevalence of Congenital Heart Defects in Monozygotic and Dizygotic Twins
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