Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation: A RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) Trial Analysis
- Airflow Obstruction, Lung Function, and Incidence of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
- Lower Levels of Sodium Intake and Reduced Cardiovascular Risk
- Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population: A Prospective Cohort Study
- Association Between Plasma Triglycerides and High-Density Lipoprotein Cholesterol and Microvascular Kidney Disease and Retinopathy in Type 2 Diabetes Mellitus: A Global Case–Control Study in 13 Countries
- Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding RNAs in Failing Human Heart and Remodeling With Mechanical Circulatory Support
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Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation: A RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) Trial Analysis
In patients with atrial fibrillation, impaired renal function is associated with a higher risk of thromboembolic events and major bleeding. Oral anticoagulation with vitamin K antagonists reduces thromboembolic events but raises the risk of bleeding. The new oral anticoagulant dabigatran has 80% renal elimination, and its efficacy and safety might, therefore, be related to renal function. In this prespecified analysis from the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, outcomes with dabigatran versus warfarin were evaluated in relation to 4 estimates of renal function, that is, equations based on creatinine levels (Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and cystatin C. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily irrespective of renal function. Rates of major bleeding were lower with dabigatran 110 mg and similar with 150 mg twice daily across the entire range of renal function. However, when the CKD-EPI or MDRD equations were used, there was a significantly greater relative reduction in major bleeding with both doses of dabigatran than with warfarin in patients with estimated glomerular filtration rate ≥80 mL/min. These findings show that dabigatran can be used with the same efficacy and adequate safety in patients with a wide range of renal function and that a more accurate estimate of renal function might be useful for improved tailoring of anticoagulant treatment in patients with atrial fibrillation and an increased risk of stroke. See p 961.
Airflow Obstruction, Lung Function, and Incidence of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Atrial fibrillation (AF) is clinically encountered during chronic obstructive pulmonary disease (COPD) exacerbations, but whether lower expiratory lung volumes (FEV1) or COPD is associated with increased risk of AF incidence was unclear. This study followed 15 004 middle-aged black and white men and women enrolled in the Atherosclerosis Risk in Communities Study (ARIC) cohort for an average of 17.5 years; 1691 (11%) developed AF. Both COPD and a reduced FEV1 at baseline were associated with a higher AF incidence independently of confounders, including smoking status. The systemic manifestations of COPD include increased sympathetic activity, systemic inflammation, and greater left ventricular mass. In addition, structural/electric abnormalities in pulmonary veins, diastolic dysfunction, low cardiac output, pulmonary hypertension, and a higher incidence of heart failure are seen with COPD. A number of the above mechanisms could alter the electrophysiological properties of cardiac atrial tissues, which in turn can trigger/sustain AF. AF is often paroxysmal and asymptomatic in nature; importantly, its first presentation could be a stroke. At other times, AF may present with symptoms resembling COPD such as uneasiness, palpitations, and dyspnea. Thus, AF should be considered for “atypical” presentations in patients with COPD or a low FEV1. AF detection through long-term ECG monitoring is increasingly accessible and affordable; however, it is not known whether screening for AF in COPD patients is warranted. See p 971.
Lower Levels of Sodium Intake and Reduced Cardiovascular Risk
Several observational studies and randomized trials have examined the associations of sodium with subsequent morbidity and mortality and generally suggest a lowering of risk with lower sodium; however, few studies have examined absolute levels of sodium intake down to recommended target intakes of 1500 to 2300 mg/d. Some recent studies have raised the possibility of adverse effects of low sodium, but these paradoxical findings might have resulted from suboptimal measurement of sodium and potential biases related to indication or reverse causation. The extended follow-up of the Trials of Hypertension Prevention (TOHP) provided the opportunity to examine the effects of low sodium intake as measured with several 24-hour sodium excretions collected over periods of 1.5 to 4 years. In this healthy cohort of 2275 prehypertensive individuals, there was a significant linear decrease in risk of cardiovascular disease with decreasing sodium levels. There was no deviation from linearity at the lowest intake levels, which suggests that cardiovascular risk continues to decline at the lowest levels of sodium intake. These data are consistent with the health benefits of reducing sodium intake to the 1500 to 2300 mg/d range in the majority of the population and are in agreement with current dietary guidelines. See p 981.
Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population: A Prospective Cohort Study
Results from the present study suggest that male pattern baldness, greying of hair, earlobe crease, xanthelasmata, and arcus corneae associate with risk of cardiovascular disease independent of age and sex. Thus, these age-related signs are not just a reflection of the chronological age of an individual, but may instead reflect the physiological state of the body, and thus be a marker of poor cardiovascular health. This is important, because it justifies the common practice for the clinician on physical examination to include a statement of whether a patient looks younger or older than his or her actual age, as an indication of the patient’s general health status. The present study further revealed that male pattern baldness, earlobe crease, and xanthelasmata are markers of ischemic heart disease independent of lipid levels and other well-known cardiovascular risk factors in addition to age and sex. Presence of these age-related signs alone—or especially in combination—should warrant further examination to make sure that these individuals are managed accordingly with regard to lifestyle changes and lipid-lowering therapy. The independent association between male pattern baldness, earlobe crease, and xanthelasmata and risk of ischemic heart disease indicates that these effects are mediated through other pathways than the classical risk factors. Further studies on the mechanisms underlying the increased risk of ischemic heart disease in individuals with these age-related signs may provide new insight into the pathogenesis of atherosclerosis, and thus may eventually reveal possible new risk factors for ischemic cardiovascular disease. See p 990.
Association Between Plasma Triglycerides and High-Density Lipoprotein Cholesterol and Microvascular Kidney Disease and Retinopathy in Type 2 Diabetes Mellitus: A Global Case–Control Study in 13 Countries
Diabetes mellitus is the major cause of renal failure and vision loss in adults. Current treatments are effective in reducing the risk of development and progression; however, the residual risk for these complications remains high. In this global case–control study of lipid risk factors for diabetic microvascular disease in 13 countries, triglycerides and high-density lipoprotein cholesterol were significantly and independently associated with diabetic microvascular disease and specifically with kidney disease. Case and control subjects were matched for low-density lipoprotein cholesterol, which averaged 2.3 mmol/L (89 mg/dL). The odds ratio for kidney disease increased by 23% for every 0.5 mmol/L (44 mg/dL) increase in triglycerides and decreased by 14% for every 0.2 mmol/L (8 mg/dL) increase in high-density lipoprotein cholesterol. The associations with retinopathy were not robust after adjustment for hypertension and hemoglobin A1c. These associations were consistent and similar in magnitude among the sites and among geographic regions (Europe, Asia, Middle East, and North America). In view of the large and growing health burden of renal failure in diabetes mellitus, these findings have considerable importance in support of additional lipid targets other than low-density lipoprotein cholesterol to benefit the diabetic population at high residual risk for microvascular disease despite current standards of care. See p 999.
Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding RNAs in Failing Human Heart and Remodeling With Mechanical Circulatory Support
Clinical management of heart failure requires reliable and accurate tools to categorize patients on the basis of underlying causes, associated risks, treatment responses, and outcomes. In recent years, myocardial transcriptional profiling has been used extensively to this end. Most prior transcriptional profiling studies in heart failure, however, examined only cardiac mRNAs or microRNAs (miRNAs), which together constitute only a small portion (≈1%) of the human genome. Because a large proportion of the genome is transcribed as long noncoding RNA (lncRNA), we profiled lncRNAs in parallel with mRNAs and miRNAs to provide a complete picture of the human cardiac transcriptome landscape in heart failure. Exploiting next-generation sequencing technology, we conducted a comprehensive cardiac transcriptome profiling study encompassing mRNAs, miRNAs, and lncRNAs in human left ventricular samples from heart failure patients before and after mechanical circulatory support with a left ventricular assist device and in left ventricular samples from nonfailing donors. We demonstrate here that the expression signature of cardiac lncRNAs compared with those of mRNAs or miRNAs provides exquisite sensitivity to discriminate cardiomyopathic samples of ischemic and nonischemic origins and to distinguish heart failure samples before and after left ventricular assist device support, revealing the potential of using lncRNA profiles as a reliable biomarker to differentiate between cardiac disease states. We further provide evidence to show that cardiac lncRNAs likely function through regulating the expression of nearby (cis) rather than distant (trans) genes. Taken together, these studies suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed after ventricular unloading with mechanical support. See p 1009.
- © 2014 American Heart Association, Inc.
- Lower Levels of Sodium Intake and Reduced Cardiovascular Risk
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